bluuebunny/crossref_metadata_2025 huggingface dataset:
Holography-guided procedural planning for modifying Venus P-valve implantation technique in patients with left pulmonary artery stents: a case-series
Authors: d’Aiello Angelo Fabio , Schianchi Laura , Bevilacqua Francesca , Ferrero Paolo , Micheletti Angelo , Negura Diana Gabriela , Pasqualin Giulia , Chessa Massimo
Published: May 2024

Background

Venus P-valve™ (Venus Medtech, Hangzhou, China) is a self-expandable bioprosthetic valve that can be transcatheter-implanted in native right ventricular outflow tract (RVOT) patients. Valve implantation is technically challenging. Due to the implantation technique, left pulmonary artery (LPA) stents represent a relative contraindication to Venus P-valve. In this case series, we describe our experience in implanting Venus P-valve in patients with previous LPA stents and the use of holographic models to facilitate procedural planning.

Methods and results

From January to October 2023, 17 patients were scheduled for Venus P-Valve implantation. 16/17 (94%) patients were successfully implanted. 3/16 (18.7%) patients underwent Venus P-valve implantation with LPA stents. All patients underwent pre-operative CT scan. CT data set were employed to create three-dimensional (3D) holographic models (Artiness, Milan, Italy) of the entire heart, which were useful to plan valve implantation with a modified technique. Procedural success rate was 100%. No procedural complications occurred. All three patients presented good haemodynamic and angiographic results at discharge and follow-up visits.

Conclusion

This case-series underscores the feasibility of Venus P-valve implantation in patients with previous LPA stents. The use of holographic models facilitated procedural planning in these challenging anatomical scenarios.
Elucidating VSMC phenotypic transition mechanisms to bridge insights into cardiovascular disease implications
Authors: Xin Yuning , Zhang Zipei , Lv Shan , Xu Shan , Liu Aidong , Li Hongyu , Li Pengfei , Han Huize , Liu Yinghui
Published: May 2024

Cardiovascular diseases (CVD) are the leading cause of death worldwide, despite advances in understanding cardiovascular health. Significant barriers still exist in effectively preventing and managing these diseases. Vascular smooth muscle cells (VSMCs) are crucial for maintaining vascular integrity and can switch between contractile and synthetic functions in response to stimuli such as hypoxia and inflammation. These transformations play a pivotal role in the progression of cardiovascular diseases, facilitating vascular modifications and disease advancement. This article synthesizes the current understanding of the mechanisms and signaling pathways regulating VSMC phenotypic transitions, highlighting their potential as therapeutic targets in cardiovascular disease interventions.
Progressive multifocal leukoencephalopathy reports in rheumatoid arthritis concerning different treatment patterns-an exploratory assessment using the food and drug administration adverse event reporting system
Authors: Honma Takeshi , Onda Kenji , Masuyama Koichi
Published: May 2024

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare but potentially life-threatening brain infection caused by the John Cunningham virus. PML is a known adverse effect associated with molecular-targeted drugs and immunosuppressive agents. Recent concerns have emerged regarding the link between methotrexate (MTX) and PML. However, limited information exists on the influence of concomitant drug use in rheumatoid arthritis (RA) treatment, where various medications are often used together.

Methods: To explore treatment patterns and patient background that affect PML reporting in RA, we analyzed data on RA cases from the Food and Drug Administration Adverse Event Reporting System (FAERS; JAPIC AERS) database between 1997 and 2019.

Results and Discussion: Our analysis revealed significantly elevated crude and adjusted reporting odds ratios (aROR) for MTX, rituximab (RIT), azathioprine, and cyclophosphamide. When considering treatment patterns, the concomitant use of MTX and RIT showed a higher aROR than using MTX or RIT alone. Additional TNF-α inhibitors or glucocorticoids did not increase PML reports. Moreover, male sex and older age were associated with increased PML reports. While limitations are inherent in studies using spontaneous reporting data, our exploratory assessment suggests an association between PML and the combination of MTX and RIT and a higher risk in men and older patients. These findings help enhance our understanding of PML risk factors in the context of RA treatment.
Interdisciplinary learning combining engravings and poems by teachers in initial training
Authors: Peña-Acuña Beatriz , Assaleh Assaleh Samir
Published: May 2024

Interdisciplinary is proposed to address a technologic knowledge-based society. This research employs quantitative methodology to analyze the perception of an integrated interdisciplinary practice involving engraving and poetry among 63 teachers in initial training. The goal is to identify correlations between age, gender, and the three dimensions of interdisciplinary. We infer a moderate positive correlation between age and the perception of skills, and a weak correlation with the perception of knowledge and interdisciplinary attitude dimensions, yielding results. This research aligns with the stance in favor of interdisciplinary education, advocating for its importance from pre-university to university levels, as a preparation for students to tackle complexity.
Online poetry writing at school – comparing lower secondary students’ experiences between individual and collaborative poetry writing
Authors: Kangasharju Arja. I. , Ilomäki Liisa , Toom Auli
Published: May 2024

Introduction

This study investigates how seventh-grade students experience online collaborative writing, its support in writing poems, and how collaboratively and individually written poems differ.

Methods

The educational design research method was used in this mixed-methods study, which was conducted in natural classroom settings to investigate students’ individual and collaborative poetry writing.

Results

The quantitative analysis of questionnaires and qualitative thematic analysis of postexperimental interviews show that the students enjoyed collaborative writing more and found it more accessible than individual writing. They experienced that it supported them in writing better poems and increased their writing confidence. They also appreciated the support of teamwork, although individual writing gave them more liberty to explore various aspects of poetry and express their feelings.

Discussion

From a pedagogical point of view, the students need to be provided with opportunities for collaborative poetry writing to make the writing process easier and more enjoyable. Online collaborative writing supports the process of poetry writing.
A novel nomogram and prognostic factor for metastatic soft tissue sarcoma survival
Authors: Han Dan , Li Bing , Xu Jie , Hu Yajie , Chen Xi , Wang Ruizhi
Published: May 2024

Background

This study represented the inaugural effort to develop predictive survival nomograms for metastatic soft tissue sarcoma (mSTS) patients in the era of immune checkpoint inhibitors.

Method

From the Surveillance, Epidemiology, and End Results (SEER) program database, we extracted 3078 eligible patients with mSTS between 2016 and 2022. Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were conducted. Subsequently, predictive nomograms were constructed. Clinical effectiveness was validated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA) methods.

Results

We used the SEER database to include 3078 eligible patients with mSTS between 2016 and 2022. All the eligible patients were randomly allocated in a ratio of 6:4 and stratified into a training group (n = 1846) and a validation group (n = 1232). In the multivariate Cox analysis, age, race, marital status, pathological grade, histologic subtype, surgery, and chemotherapy were identified as independent prognostic factors. These factors were used to construct the nomogram to predict the 1-, 3-, and 5-year OS of mSTS patients. The C-index for the training cohort and the validation cohort was 0.722(95% confidence interval [CI]: 0.708–0.736), and 0.716(95% CI: 0.698–0.734), respectively. The calibration curves for 1-, 3-, and 5-year OS probability demonstrated excellent calibration between the predicted and the actual survival. The AUC values of the nomogram at 1-, 3-, and 5-year were 0.785, 0.767, and 0.757 in the training cohort, 0.773, 0.754, and 0.751 in the validation cohort, respectively. Furthermore, DCA indicated the favorable clinical utility of the nomogram in both cohorts. The risk stratification system was constructed using the established nomogram, which enhanced prediction accuracy, aided clinicians in identifying high-risk patients and informing treatment decisions.

Conclusion

This study marked the inaugural effort in constructing predictive survival nomograms mSTS patients in the era of immune checkpoint inhibitors. The robustly constructed nomograms, alongside actual outcomes, offered valuable insights to inform follow-up management strategies.
The progress of clinical research on the detection of 1,5-anhydroglucitol in diabetes and its complications
Authors: Xu Huijuan , Pan Junhua , Chen Qiu
Published: May 2024

1,5-Anhydroglucitol (1,5-AG) is sensitive to short-term glucose fluctuations and postprandial hyperglycemia, which has great potential in the clinical application of diabetes as a nontraditional blood glucose monitoring indicator. A large number of studies have found that 1,5-AG can be used to screen for diabetes, manage diabetes, and predict the perils of diabetes complications (diabetic nephropathy, diabetic cardiovascular disease, diabetic retinopathy, diabetic pregnancy complications, diabetic peripheral neuropathy, etc.). Additionally, 1,5-AG and β cells are also associated with each other. As a noninvasive blood glucose monitoring indicator, salivary 1,5-AG has much more benefit for clinical application; however, it cannot be ignored that its detection methods are not perfect. Thus, a considerable stack of research is still needed to establish an accurate and simple enzyme assay for the detection of salivary 1,5-AG. More clinical studies will also be required in the future to confirm the normal reference range of 1,5-AG and its role in diabetes complications to further enhance the blood glucose monitoring system for diabetes.
Causal relationship between type 2 diabetes mellitus and aortic dissection: insights from two-sample Mendelian randomization and mediation analysis
Authors: Zhang Weizong , Sun Jindong , Yu Huamin , Shi Minjuan , Hu Haiqiang , Yuan Hong
Published: May 2024

Objective

Some evidence suggests a reduced prevalence of type 2 diabetes mellitus (T2DM) in patients with aortic dissection (AD), a catastrophic cardiovascular illness, compared to general population. However, the conclusions were inconsistent, and the causal relationship between T2DM and AD remains unclear.

Methods

In this study, we aimed to explore the causal relationship between T2DM and AD using bidirectional Mendelian randomization (MR) analysis. Mediation MR analysis was conducted to explore and quantify the possible mediation effects of 1400 metabolites in T2DM and AD.

Results

The results of 26 datasets showed no causal relationship between T2DM and AD (P>0.05). Only one dataset (ebi-a-GCST90006934) showed that T2DM was a protective factor for AD (I9-AORTDIS) (OR=0.815, 95%CI: 0.692-0.960, P=0.014), and did not show horizontal pleiotropy (P=0.808) and heterogeneity (P=0.525). Vanillic acid glycine plays a mediator in the causal relationship between T2DM and AD. The mediator effect for vanillic acid glycine levels was -0.023 (95%CI: -0.066-0.021).

Conclusion

From the perspective of MR analysis, there might not be a causal relationship between T2DM and AD, and T2DM might not be a protective factor for AD. If a causal relationship does exist between T2DM and AD, with T2DM serving as a protective factor, vanillic acid glycine may act as a mediator and enhance such a protective effect.
Detailed analysis of skull morphology and brain size in crested Padovana chicken (Gallus gallus f.d.)
Authors: Wolf-Vollenbröker Michael , Petow Stefanie , Schmidbauer Max , Fellmin Mareike , Ulrich Reiner , Mehlhorn Julia
Published: May 2024

Introduction

Crested chickens show abnormalities in their anatomy of the skull, endocranium, and brain (including cerebral elongation) and can be appropriate model systems for neuroanatomical evolution, brain–skull integration, and skull and brain deformities. Here, we give a detailed comprehensive description of the skull of crested chickens using the example of the Padovana chicken, including ontogenetic aspects and an allometric analysis of their brain size.

Methods

In total, 109 chickens of two different strains of the Padovana chicken were hatched together. All animals were X-rayed weekly during growth. Nine juvenile (ready for hatch) and 22 adult skulls were processed for histology and morphological descriptions, and a further 20 individuals were processed for brain analysis.

Results

At hatching, all chicks were already crested, and a distinctive bony protuberance was first observed at the age of 4 weeks. Juvenile chickens exhibit either an open neurocranium or a protuberance. In the adult skull, foramina of different sizes can be found in the frontal bone, but no completely open neurocrania are observed in juveniles. Particularly in Padovana with cranial protuberances, several peculiarities can be observed in the os mesethmoidale, os nasale, os praemaxillare, orbit, and cranial fossae. Additionally, the brain of Padovana with cranial protuberances looks drawn in length with the shape of an hourglass and showed significantly larger encephalization indices than plain-headed breeds, topped only by another crested chicken breed.

Discussion

Investigations on chickens with cerebral elongation may facilitate the understanding of skull and brain dysplasia and may provide meaningful insights into cerebral hernia development. Additionally, crested breeds, combined with standard chickens, form a promising comparative system for investigating the emergence of novel brain and skull morphologies.
The regulation and potential role of interleukin-32 in tuberculous pleural effusion
Authors: Wang Xuan , Yang Chengqing , Quan Chao , Li Jun , Hu Yan , Liu Peng , Guan Lulu , Li Li
Published: May 2024

The possible protective effect of interleukin-32 (IL-32) in Mycobacterium tuberculosis (Mtb) infection has been indicated. However, few studies have been focused on IL-32 in tuberculosis patients. Additionally, the regulation of IL-32 production has rarely been reported. In the present study, the production, regulation, and role of IL-32 in tuberculous pleurisy (TBP) were investigated. We found that the content of IL-32 in tuberculous pleural effusion (TPE) was higher than the level in the malignant pleural effusion and transudative pleural effusion. The level of IL-32 mRNA in pleural fluid mononuclear cells (PFMCs) was higher than that in peripheral blood mononuclear cells (PBMCs) of patients with TBP, and this difference was mainly reflected in the splice variants of IL-32α, IL-32β, and IL-32γ. Compared with the PBMCs, PFMCs featured higher IL-32β/IL-32γ and IL-32α/IL-32γ ratios. In addition, lipopolysaccharide (LPS), Bacillus Calmette-Guérin (BCG), and H37Ra stimulation could induce IL-32 production in the PFMCs. IL-32 production was positively correlated with the TNF-α, IFN‐γ, and IL-1Ra levels in TPE, whereas IFN-γ, but not TNF-α or IL-1Ra, could induce the production of IL-32 in PFMCs. Furthermore, IL-32γ could induce the TNF-α production in PFMCs. Monocytes and macrophages were the main sources of IL-32 in PFMCs. Nevertheless, direct cell–cell contact between lymphocytes and monocytes/macrophages plays an important role in enhancing IL-32 production by monocyte/macrophage cells. Finally, compared with the non-tuberculous pleural effusion, the purified CD4+ and CD8+ T cells in TPE expressed higher levels of intracellular IL-32. Our results suggested that, as a potential biomarker, IL-32 may play an essential role in the protection against Mtb infection in patients with TBP. However, further studies need to be carried out to clarify the functions and mechanisms of the IFN-γ/IL-32/TNF-α axis in patients with TBP.
Tumor cells express and maintain HMGB1 in the reduced isoform to enhance CXCR4-mediated migration
Authors: Pirani Edisa , Paparoditis Philipp , Pecoraro Matteo , Danelon Gabriela , Thelen Marcus , Cecchinato Valentina , Uguccioni Mariagrazia
Published: May 2024

During inflammation and tissue regeneration, the alarmin High Mobility Group Box 1 (HMGB1), in its reduced isoform, enhances the activity of the chemokine CXCL12, forming a heterocomplex that acts via the chemokine receptor CXCR4. Despite the established roles of both HMGB1 and CXCL12 in tumor progression and metastatic spread to distal sites, the role of the CXCL12/HMGB1 heterocomplex in cancer has never been investigated. By employing a newly established mass spectrometry protocol that allows an unambiguous distinction between reduced (red-HMGB1) and oxidized (ox-HMGB1) HMGB1 isoforms in cell lysates, we demonstrate that human epithelial cells derived from breast (MCF-7 and MDA-MB-231) and prostate (PC-3) cancer predominantly express red-HMGB1, while primary CD3+ T lymphocytes from peripheral blood express both HMGB1 isoforms. All these cancer cells release HMGB1 in the extracellular microenvironment together with varying concentrations of thioredoxin and thioredoxin reductase. The CXCL12/HMGB1 heterocomplex enhances, via CXCR4, the directional migration and invasiveness of cancer cells characterized by high metastatic potential that possess a fully active thioredoxin system, contributing to maintain red-HMGB1. On the contrary, cancer cells with low metastatic potential, lack thioredoxin reductase, promptly uptake CXCL12 and fail to respond to the heterocomplex. Our study demonstrates that the responsiveness of cancer cells to the CXCL12/HMGB1 heterocomplex, resulting in enhanced cell migration and invasiveness, depends on the maintenance of HMGB1 in its reduced isoform, and suggests disruption of the heterocomplex as a potential therapeutic target to inhibit invasion and metastatic spread in cancer therapies.
Polish regulatory system regarding ATMP hospital exemptions
Authors: Pachocki Jan , Verter Frances
Published: May 2024

Introduction

This article explains the current regulatory system in Poland regarding Advanced Therapy Medicinal Products given under Hospital Exemptions (ATMP-HE).

Methods

The relevant sections of Polish legislation are translated into English and their interaction is described.

Results

We analyze the impact of these regulations from the perspective of three stakeholder groups: manufacturers, physicians, and patients. Amendments enacted between 2018 and 2023 have substantially changed Polish implementation of the ATMP-HE pathway. In Poland, most ATMP-HE treatments have been therapies employing Mesenchymal Stromal Cells (MSC).

Discussion

Comparison to other European countries shows that Poland is within the mainstream of EU practices regarding ATMP-HE implementation. One notable issue is that Poland has relatively low per capita spending on healthcare, and ATMP-HE in Poland must be funded from outside the government healthcare system. Conclusions. The original intention of the legislation that created ATMP-HE was to allow access to experimental therapies for patients with unmet needs. It remains to be seen if that mission can be fulfilled amidst conflicting pressures from various stakeholder groups.
Top predator status and trends: ecological implications, monitoring and mitigation strategies to promote ecosystem-based management
Authors: Fortuna Caterina Maria , Fortibuoni Tomaso , Bueno-Pardo Juan , Coll Marta , Franco Anita , Giménez Joan , Stranga Yolanda , Peck Myron A. , Claver Cristina , Brasseur Sophie , Fernández-Corredor Elena , Fraschetti Simonetta , Garcia-Garin Odei , van Leeuwen Anieke , Louzao Maite , Pedrajas Arkaitz , Raicevich Saša , Ramírez Francisco , Ransijn Janneke , Russell Debbie , Serena Fabrizio , Sbragaglia Valerio , Katsanevakis Stelios
Published: May 2024

The conservation and management of marine ecosystems hinge on a comprehensive understanding of the status and trends of top predators. This review delves into the ecological significance of marine top predators, examining their roles in maintaining ecosystem stability and functioning through an integrated analysis of current scientific literature. We first assess the efficacy of various monitoring methods, ranging from traditional field observations to cutting-edge technologies like satellite tracking and environmental DNA (eDNA) analysis and evaluating their strengths and limitations in terms of accuracy, spatial coverage, and cost-effectiveness, providing resource managers with essential insights for informed decision-making. Then, by synthesizing data from diverse marine ecosystems, this study offers a comprehensive overview of the trends affecting top predator populations worldwide. We explore the multifaceted impacts of human activities, climate change, and habitat degradation on the abundance and distribution of these key species. In doing so, we shed light on the broader implications of declining top predator populations, such as trophic cascades and altered community structures. Following a thorough assessment of successful strategies for reversing the decline of top predators, a compilation of recommendations is presented, encompassing effective governance interventions. A crucial aspect of effective ecosystem-based management is the implementation of robust monitoring strategies. Mitigation measures are imperative to reverse the adverse impacts on marine top predators. We present a comprehensive array of mitigation options based on successful case studies. These include the establishment of marine protected areas, the enforcement of fisheries regulations, and the promotion of sustainable fishing practices. We deepen the synergies between these strategies and their potential to mitigate human-induced stressors on top predator populations to safeguard their pivotal role in maintaining marine ecosystem structure and function. By examining marine top predators’ ecological significance, analyzing population trends, discussing monitoring techniques, and outlining effective mitigation strategies, we provide a comprehensive resource for researchers, policymakers, and stakeholders engaged in fostering ecosystem-based management approaches. We conclude that integrating these insights into current management frameworks will be essential to safeguard both top predators and the broader marine environment for future generations.
Decomposition in an extreme cold environment and associated microbiome—prediction model implications for the postmortem interval estimation
Authors: Iancu Lavinia , Bonicelli Andrea , Procopio Noemi
Published: May 2024

Introduction

The accurate estimation of postmortem interval (PMI), the time between death and discovery of the body, is crucial in forensic science investigations as it impacts legal outcomes. PMI estimation in extremely cold environments becomes susceptible to errors and misinterpretations, especially with prolonged PMIs. This study addresses the lack of data on decomposition in extreme cold by providing the first overview of decomposition in such settings. Moreover, it proposes the first postmortem microbiome prediction model for PMI estimation in cold environments, applicable even when the visual decomposition is halted.

Methods

The experiment was conducted on animal models in the second-coldest region in the United States, Grand Forks, North Dakota, and covered 23 weeks, including the winter months with temperatures as low as −39°C. Random Forest analysis models were developed to estimate the PMI based either uniquely on 16s rRNA gene microbial data derived from nasal swabs or based on both microbial data and measurable environmental parameters such as snow depth and outdoor temperatures, on a total of 393 samples.

Results

Among the six developed models, the best performing one was the complex model based on both internal and external swabs. It achieved a Mean Absolute Error (MAE) of 1.36 weeks and an R2 value of 0.91. On the other hand, the worst performing model was the minimal one that relied solely on external swabs. It had an MAE of 2.89 weeks and an R2 of 0.73. Furthermore, among the six developed models, the commonly identified predictors across at least five out of six models included the following genera: Psychrobacter (ASV1925 and ASV1929), Carnobacterium (ASV2872) and Pseudomonas (ASV1863).

Discussion

The outcome of this research provides the first microbial model able to predict PMI with an accuracy of 9.52 days over a six-month period of extreme winter conditions.
CT texture analysis of vertebrobasilar artery calcification to identify culprit plaques
Authors: Liu Bo , Xue Chen , Lu Haoyu , Wang Cuiyan , Duan Shaofeng , Yang Huan
Published: May 2024

Objectives

The aim of this study was to extract radiomic features from vertebrobasilar artery calcification (VBAC) on head computed tomography (CT) images and investigate its diagnostic performance to identify culprit lesions responsible for acute cerebral infarctions.

Methods

Patients with intracranial atherosclerotic disease who underwent vessel wall MRI (VW-MRI) and head CT examinations from a single center were retrospectively assessed for VBAC visual and textural analyses. Each calcified plaque was classified by the likelihood of having caused an acute cerebral infarction identified on VW-MRI as culprit or non-culprit. A predefined set of texture features extracted from VBAC segmentation was assessed using the minimum redundancy and maximum relevance method. Five key features were selected to integrate as a radiomic model using logistic regression by the Aikaike Information Criteria. The diagnostic value of the radiomic model was calculated for discriminating culprit lesions over VBAC visual assessments.

Results

A total of 1,218 radiomic features were extracted from 39 culprit and 50 non-culprit plaques, respectively. In the VBAC visual assessment, culprit plaques demonstrated more observed presence of multiple calcifications, spotty calcification, and intimal predominant calcification than non-culprit lesions (all p < 0.05). In the VBAC texture analysis, 55 (4.5%) of all extracted features were significantly different between culprit and non-culprit plaques (all p < 0.05). The radiomic model incorporating 5 selected features outperformed multiple calcifications [AUC = 0.81 with 95% confidence interval (CI) of 0.72, 0.90 vs. AUC = 0.61 with 95% CI of 0.49, 0.73; p = 0.001], intimal predominant calcification (AUC = 0.67 with 95% CI of 0.58, 0.76; p = 0.04) and spotty calcification (AUC = 0.62 with 95% CI of 0.52, 0.72; p = 0.005) in the identification of culprit lesions.

Conclusion

Culprit plaques in the vertebrobasilar artery exhibit distinct calcification radiomic features compared to non-culprit plaques. CT texture analysis of VBAC has potential value in identifying lesions responsible for acute cerebral infarctions, which may be helpful for stroke risk stratification in clinical practice.
An optimized framework for processing multicentric polysomnographic data incorporating expert human oversight
Authors: Holm Benedikt , Jouan Gabriel , Hardarson Emil , Sigurðardottir Sigríður , Hoelke Kenan , Murphy Conor , Arnardóttir Erna Sif , Óskarsdóttir María , Islind Anna Sigríður
Published: May 2024

Introduction

Polysomnographic recordings are essential for diagnosing many sleep disorders, yet their detailed analysis presents considerable challenges. With the rise of machine learning methodologies, researchers have created various algorithms to automatically score and extract clinically relevant features from polysomnography, but less research has been devoted to how exactly the algorithms should be incorporated into the workflow of sleep technologists. This paper presents a sophisticated data collection platform developed under the Sleep Revolution project, to harness polysomnographic data from multiple European centers.

Methods

A tripartite platform is presented: a user-friendly web platform for uploading three-night polysomnographic recordings, a dedicated splitter that segments these into individual one-night recordings, and an advanced processor that enhances the one-night polysomnography with contemporary automatic scoring algorithms. The platform is evaluated using real-life data and human scorers, whereby scoring time, accuracy, and trust are quantified. Additionally, the scorers were interviewed about their trust in the platform, along with the impact of its integration into their workflow.

Results

We found that incorporating AI into the workflow of sleep technologists both decreased the time to score by up to 65 min and increased the agreement between technologists by as much as 0.17 κ.

Discussion

We conclude that while the inclusion of AI into the workflow of sleep technologists can have a positive impact in terms of speed and agreement, there is a need for trust in the algorithms.
Expression of the apelin receptor, a novel potential therapeutic target, and its endogenous ligands in diverse stem cell populations in human glioblastoma
Authors: Williams Thomas L. , Nwokoye Peter , Kuc Rhoda E. , Smith Kieran , Paterson Anna L. , Allinson Kieren , Maguire Janet J. , Davenport Anthony P.
Published: May 2024

Glioblastoma multiforme (GBM) is one of the most common and lethal forms of brain cancer, carrying a very poor prognosis (median survival of ~15 months post-diagnosis). Treatment typically involves invasive surgical resection of the tumour mass, followed by radiotherapy and adjuvant chemotherapy using the alkylating agent temozolomide, but over half of patients do not respond to this drug and considerable resistance is observed. Tumour heterogeneity is the main cause of therapeutic failure, where diverse progenitor glioblastoma stem cell (GSC) lineages in the microenvironment drive tumour recurrence and therapeutic resistance. The apelin receptor is a class A GPCR that binds two endogenous peptide ligands, apelin and ELA, and plays a role in the proliferation and survival of cancer cells. Here, we used quantitative whole slide immunofluorescent imaging of human GBM samples to characterise expression of the apelin receptor and both its ligands in the distinct GSC lineages, namely neural-progenitor-like cells (NPCs), oligodendrocyte-progenitor-like cells (OPCs), and mesenchymal-like cells (MES), as well as reactive astrocytic cells. The data confirm the presence of the apelin receptor as a tractable drug target that is common across the key cell populations driving tumour growth and maintenance, offering a potential novel therapeutic approach for patients with GBM.
The NDR family of kinases: essential regulators of aging
Authors: Jonischkies Kevin , del Angel Miguel , Demiray Yunus Emre , Loaiza Zambrano Allison , Stork Oliver
Published: May 2024

Aging is defined as a progressive decline of cognitive and physiological functions over lifetime. Since the definition of the nine hallmarks of aging in 2013 by López-Otin, numerous studies have attempted to identify the main regulators and contributors in the aging process. One interesting group of proteins whose participation has been implicated in several aging hallmarks are the nuclear DBF2-related (NDR) family of serine-threonine AGC kinases. They are one of the core components of the Hippo signaling pathway and include NDR1, NDR2, LATS1 and LATS2 in mammals, along with its highly conserved metazoan orthologs; Trc in Drosophila melanogaster, SAX-1 in Caenorhabditis elegans, CBK1, DBF20 in Saccharomyces cerevisiae and orb6 in Saccharomyces pombe. These kinases have been independently linked to the regulation of widely diverse cellular processes disrupted during aging such as the cell cycle progression, transcription, intercellular communication, nutrient homeostasis, autophagy, apoptosis, and stem cell differentiation. However, a comprehensive overview of the state-of-the-art knowledge regarding the post-translational modifications of and by NDR kinases in aging has not been conducted. In this review, we summarize the current understanding of the NDR family of kinases, focusing on their relevance to various aging hallmarks, and emphasize the growing body of evidence that suggests NDR kinases are essential regulators of aging across species.
Efficacy and safety of stereotactic radiotherapy on elderly patients with stage I-II central non-small cell lung cancer
Authors: Ji Xiaoqin , Zhou Bin , Huang Hua , Wang Yong , Jiang Wanrong , Wang Jiasheng , Ding Wei , Wang Zhen , Chen Guanha , Sun Xiangdong
Published: May 2024

Background

Many studies demonstrated the safety and efficacy of SBRT in the treatment of elderly patients with early-stage non-small cell lung cancer (NSCLC). However, those studies focused on patients with peripheral lung cancer. This study aimed to evaluate the clinical efficacy and toxicity of SBRT in elderly patients with stage I-II central NSCLC in single institution.

Methods

From April 2009 to January 2020, a retrospective study was conducted on patients ≥ 65 years old with stage I-II NSCLC that was centrally localized and treated with SBRT at a single institution. Absolute C-reactive protein (CRP)/albumin ratio (CAR) and body mass index (BMI) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), cancer-specific death, noncancer-specific death, local progression (LP) and distant progression (DP).

Results

Stereotactic body radiation treatment (SBRT) was administered to a total of 44 patients. The most common dose fractionation schedule was 60 Gy given in 5 fractions. The median PFS of the cohort was 31 months (95% CI, 19.47–42.53 months). The median OS of all patients was 69 months (95% CI, 33.8–104.2 months). The median time to noncancer-specific death was 54.5 months. The median time to cancer-specific death was 36 months. The cumulative incidences of cancer-specific death at 1 year, 5 years, and 10 years were 11.63% (95%CI, 4.2–23.23%), 42.99% (95%CI, 27.56–57.53%), and 65.94% (95%CI, 45.76–80.1%), respectively. pre-SBRT BMI of ≤ 22.77 (HR 4.60, 95% CI 1.84–11.51, P=0.001) and pre-SBRT CAR of ≤0.91 (HR 5.19, 95% CI 2.15–12.52, P<0.000) were significant predictors of higher OS on multivariable analysis. The median times to LP and DP were 10 months and 11 months, respectively. In terms of acute toxicity, grade 1 including cough (38.64%), radiation pneumonitis (29.55%), anemia (25%), and fatigue (20.45%) was often observed. There was no evidence of grade 4 or 5 acute toxicity. In terms of late toxicity, 2 patients developed grade 1 pulmonary fibrosis during follow-up.

Conclusion

This study showed that SBRT can effectively control local tumor progression, and have acceptable toxicity for elderly patients with centrally located stage I-II NSCLC. Lower pre-SBRT BMI and lower pre-SBRT CAR were associated with a decreased risk of cancer-specific death.
Myofibroblastic sarcoma in breast: a case report and literature review
Authors: Deng Zixi , Xia Chuan , Li Yuechong , Luo Yongchao , Shen Songjie
Published: May 2024

Myofibroblastic sarcoma is a malignancy in which myofibroblasts are the main component, with a very low incidence. In this study, we report a case of low-grade myofibroblastic sarcoma (LGMS) in the breast. After the diagnosis of LGMS, the patient received a mastectomy. The patient showed no relapse or progression during the follow-up time of 3 months following the operation. LGMS in the breast is extremely rare, and the limited experience with its diagnosis and treatment brings obstacles to doctors. Therefore, this report summarizes the preoperative diagnosis, treatment, and prognosis of breast LGMS through a literature review.
Diagnostic performance of volatile organic compounds analysis and electronic noses for detecting colorectal cancer: a systematic review and meta-analysis
Authors: Wang Qiaoling , Fang Yu , Tan Shiyan , Li Zhuohong , Zheng Ruyi , Ren Yifeng , Jiang Yifang , Huang Xiaopeng
Published: May 2024

Introduction

The detection of Volatile Organic Compounds (VOCs) could provide a potential diagnostic modality for the early detection and surveillance of colorectal cancers. However, the overall diagnostic accuracy of the proposed tests remains uncertain.

Objective

This systematic review is to ascertain the diagnostic accuracy of using VOC analysis techniques and electronic noses (e-noses) as noninvasive diagnostic methods for colorectal cancer within the realm of clinical practice.

Methods

A systematic search was undertaken on PubMed, EMBASE, Web of Science, and the Cochrane Library to scrutinize pertinent studies published from their inception to September 1, 2023. Only studies conducted on human subjects were included. Meta-analysis was performed using a bivariate model to obtain summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was deployed for quality assessment. The protocol for this systematic review was registered in PROSPERO, and PRISMA guidelines were used for the identification, screening, eligibility, and selection process.

Results

This review encompassed 32 studies, 22 studies for VOC analysis and 9 studies for e-nose, one for both, with a total of 4688 subjects in the analysis. The pooled sensitivity and specificity of VOC analysis for CRC detection were 0.88 (95% CI, 0.83-0.92) and 0.85 (95% CI, 0.78-0.90), respectively. In the case of e-nose, the pooled sensitivity was 0.87 (95% CI, 0.83-0.90), and the pooled specificity was 0.78 (95% CI, 0.62-0.88). The area under the receiver operating characteristic analysis (ROC) curve for VOC analysis and e-noses were 0.93 (95% CI, 0.90-0.95) and 0.90 (95% CI, 0.87-0.92), respectively.

Conclusion

The outcomes of this review substantiate the commendable accuracy of VOC analysis and e-nose technology in detecting CRC. VOC analysis has a higher specificity than e-nose for the diagnosis of CRC and a sensitivity comparable to that of e-nose. However, numerous limitations, including a modest sample size, absence of standardized collection methods, lack of external validation, and a notable risk of bias, were identified. Consequently, there exists an imperative need for expansive, multi-center clinical studies to elucidate the applicability and reproducibility of VOC analysis or e-nose in the noninvasive diagnosis of colorectal cancer.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023398465.
Case Report: A rare infection of multidrug-resistant Aeromonas caviae in a pediatric case with acute lymphoblastic leukemia and review of the literature
Authors: Dai Yiling , Gao Ju , Jiang Mingyan
Published: May 2024

Aeromonas caviae infection of the bloodstream and intestine is a rare and severe opportunistic infection in immunocompromised people. In Southwest China, we first reported a case of bloodstream and intestinal infection with multidrug-resistant (MDR) Aeromonas caviae in a 4-year-old child with T-cell acute lymphoblastic leukemia. Blood and stool cultures were used to identify the infection. The selection of antibiotics was based on clinical expertise and medication sensitivity tests. We used linezolid, levofloxacin, and polymyxin B to treat the patient aggressively. Aeromonas caviae infection is uncommon in juvenile acute lymphoblastic leukemia. Doctors should be aware of the likelihood of opportunistic infection during the post-chemotherapy bone marrow suppression period. We further conducted a review of the literature and performed a detailed analysis of Aeromonas infection in pediatric leukemia. It is becoming increasingly apparent that antibiotic is abused domestically and abroad, resulting in the sharp increase of MDR bacteria. In general, most of the Aeromonas isolates are susceptible to third- or fourth-generation cephalosporins, aminoglycosides, quinolones, and carbapenem, but drug-resistant strains are being reported increasingly. We summarized the drug resistance rate of Aeromonas caviae and Aeromonas hydrophila in China in the last 10 years. Early recognition and effective treatment will improve prognosis and reduce mortality.
Case Report: The importance of early intervention for gastroesophageal reflex disease caused by hiatal hernia
Authors: Kakiuchi Toshihiko , Obata Satoshi , Koji Azusa , Minematsu Nobuya , Fuchigami Maho , Fukuta Atsuhisa , Tajiri Tatsuro , Yoshiura Masato
Published: May 2024

Background

Gastroesophageal reflux (GER) disease (GERD) is a condition wherein GER causes troublesome symptoms that can affect daily functioning and/or clinical complications within the esophagus or other systems. To avoid this, patients with GERD often require treatment; hence, it is important to distinguish GER from GERD. Patients with GERD exhibiting alarm signs should be examined early to differentiate it from GER and treated accordingly. Herein, we present a case of GERD caused by a hiatal hernia that required surgical intervention for esophagial cicatrical stenosis despite oral treatment. We also discussed how to choose the appropriate acid suppressants for GERD.

Case presentation

A 1-year-old boy was referred to our hospital for repeated vomiting and poor weight gain. He received histamine 2 receptor antagonists (H2RAs) that contributed slightly to the decreased frequency of vomiting and aided weight gain; however, he soon stopped gaining weight and had bloody vomit. His upper gastrointestinal series revealed hiatal hernia, a 24 h impedance pH monitoring test indicated abnormal values for acid reflux, and esophagogastroduodenoscopy (EGD) revealed esophagitis. He was subsequently diagnosed with GERD associated with hiatal hernia. A proton pump inhibitor (PPI) was intravenously administered to him, following which his medication was changed to a potassium-competitive acid blocker (P-CAB). Thereafter, his vomiting episodes significantly decreased and his weight increased. However, 6 months after starting P-CAB, his vomiting episodes suddenly increased in frequency. EGD revealed the presence esophageal stricture due to scarring from GERD. He was then treated via laparoscopic fundoplication, gastrostomy, and esophageal balloon dilation. Thereafter, his vomiting episodes stopped and food intake improved, leading to weight gain.

Conclusion

It is essential to identify the cause of GERD early and take an appropriate treatment approach depending on the cause of GERD with alarm signs. Further, as a drug therapy for GERD as a clear acid mediated disease or in children with alarm signs, PPIs or P-CAB should be used from the beginning instead of H2RAs.
Decoction derived from Allium ascalonicum L. bulbs and Sojae Semen Praeparatum alleviates wind-cold-type common cold via Nrf2/HO-1 pathway and modulation of Lactobacillus murinus level
Authors: Jiang Yuanyuan , Wei Wenfeng , Zhou Jiaxin , Qiu Shixian , Yang Qixin , Huo Jin hai , Wang Weiming
Published: May 2024

Background

Cong-Chi decoction (CCD) is made using Allium ascalonicum L. (shallot) bulbs and Sojae Semen Praeparatum (SSP). Shallot bulbs and SSP are both used regularly in traditional Chinese medicine; however, there are no recent pharmacological studies on their synergistic effects. Despite their roles in the treatment of the common cold for thousands of years, their pharmacological mechanisms of action against wind-cold-type common cold are yet to be explored comprehensively.

Methods

A mouse model was standardized using wind-cold modeling equipment to study the anti-inflammatory, antioxidant, and antiapoptotic effects of CCD. Then, 16S rRNA sequencing was employed to analyze the association between Lactobacillus murinus and changes in body temperature. Additionally, the antipyretic effects of L. murinus were validated via animal experiments.

Results

The results indicate that CCD improves the symptoms of wind-cold by reducing fever, levels of pro-inflammatory factors, and cellular apoptosis, as well as increasing the blood leukocyte and lymphocyte counts, thereby alleviating lung tissue damage. The effects of CCD are mediated by upregulation of pulmonary Nrf2 and HO-1 expressions, thereby reducing oxidative damage in the lungs, in addition to other anti-inflammatory mechanisms. Furthermore, CCD increases the abundance of L. murinus in the intestinal tract. The animal experiments confirm that L. murinus ameliorates fever in mice.

Conclusion

CCD exhibits remarkable antioxidant and anti-inflammatory properties for effectively treating wind-cold-type common cold. Furthermore, its regulatory effects on L. murinus represent a novel mechanism for product development.
Animal-derived natural products for hepatocellular carcinoma therapy: current evidence and future perspectives
Authors: Liao Yichao , Wei Feng , He Zhelin , He Jingxue , Ai Yanlin , Guo Cui , Zhou Li , Luo Dan , Li Chengen , Wen Yueqiang , Zeng Jinhao , Ma Xiao
Published: May 2024

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate, and the survival rate of HCC patients remains low. Animal medicines have been used as potential therapeutic tools throughout the long history due to their different structures of biologically active substances with high affinity to the human body. Here, we focus on the effects and the mechanism of action of animal-derived natural products against HCC, which were searched in databases encompassing Web of Science, PubMed, Embase, Science Direct, Springer Link, and EBSCO. A total of 24 natural products from 12 animals were summarized. Our study found that these natural products have potent anti-hepatocellular carcinoma effects. The mechanism of action involving apoptosis induction, autophagy induction, anti-proliferation, anti-migration, and anti-drug resistance via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Ras/extracellular signal regulated kinases (ERK)/mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Huachansu injection and sodium cantharidate have been used in clinical applications with good efficacy. We review the potential of animal-derived natural products and their derivatives in the treatment of HCC to date and summarize their application prospect and toxic side effects, hoping to provide a reference for drug development for HCC.
Exposure therapy tailored to inhibitory learning principles in a naturalistic setting: an open pilot trial in obsessive-compulsive outpatient care
Authors: Kühne Franziska , Hobrecker Lea Kathrin , Heinze Peter Eric , Meißner Claudia , Weck Florian
Published: May 2024

Inhibitory learning (IL) theory offers promising therapeutic strategies. However, more evidence is needed, especially regarding OCD treatment in routine care. The present pilot study investigated the positive and negative effects of IL-focused cognitive-behavioral therapy (CBT) in a university outpatient setting. A total of N = 21 patients (57.14% male, mean age 31.14, SD = 12.39 years) passed through manualized therapy delivered by licensed psychotherapists. Between the first and 20th IL-focused CBT session, obsessive-compulsive symptoms (Obsessive Compulsive Inventory-Revised, d = 3.71), obsessive beliefs (Obsessive-Beliefs Questionnaire, d = 1.17), depressive symptoms (Beck Depression Inventory, d = 3.49), and overall psychological distress (Global Severity Index, d = 3.40) decreased significantly (all ps < 0.01). However, individual patients reported some negative effects of therapy. The results underline the value of thorough investigations of novel therapeutic interventions in naturalistic settings.