bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Coherence Tomography–Based Functional Stenosis Assessment: FUSION—A Prospective Multicenter Trial
Authors: Jeremias Allen , Maehara Akiko , Matsumura Mitsuaki , Shlofmitz Richard A. , Maksoud Aziz , Akasaka Takashi , Bezerra Hiram G. , Fearon William F. , Samady Habib , Samuels Bruce , Rapkin Joshua , Gopinath Ajay , Teraphongphom Nutte Tarn , Buccola Jana , Ali Ziad A.
Published: March 2024

BACKGROUND:

Intravascular imaging and intracoronary physiology may both be used to guide and optimize percutaneous coronary intervention; however, they are rarely used together. The virtual flow reserve (VFR) is an optical coherence tomography (OCT)–based model of fractional flow reserve (FFR) facilitating the assessment of the physiological significance of coronary lesions. We aimed to validate the VFR assessment of intermediate coronary artery stenoses.

METHODS:

FUSION (Validation of OCT-Based Functional Diagnosis of Coronary Stenosis) was a multicenter, prospective, observational study comparing OCT-derived VFR to invasive FFR. VFR was mathematically derived from a lumped parameter flow model based on 3-dimensional lumen morphology. Patients undergoing coronary angiography with intermediate angiographic stenosis (40%–90%) requiring physiological assessment were enrolled. Investigational sites were blinded to the VFR analysis, and all OCT and FFR data were reviewed by an independent core laboratory. The coprimary end points were the sensitivity and specificity of VFR against FFR as the reference standard, each of which was tested against prespecified performance goals.

RESULTS:

After core laboratory review, 266 vessels in 224 patients from 25 US centers were included in the analysis. The mean angiographic diameter stenosis was 65.5%±14.9%, and the mean FFR was 0.83±0.11. Overall accuracy, sensitivity, and specificity of VFR versus FFR using a binary cutoff point of 0.80 were 82.0%, 80.4%, and 82.9%, respectively. The 97.5% lower confidence bound met the prespecified performance goal for sensitivity (71.6% versus 70%;
P
=0.01) and specificity (76.6% versus 75%;
P
=0.01). The area under the curve was 0.88 (95% CI, 0.84–0.92;
P
<0.0001).

CONCLUSIONS:

OCT-derived VFR demonstrates high sensitivity and specificity for predicting invasive FFR. Integrating high-resolution intravascular imaging with imaging-derived physiology may provide synergistic benefits as an adjunct to percutaneous coronary intervention.

REGISTRATION:

URL:
https://clinicaltrials.gov
; Unique identifier: NCT04356027.
Lyophyllum lixivium (Lyophyllaceae, Agaricales), a new species from Yunnan, China
Authors: LYU TONG , TANG SONG-MING , HE JUN , WANG SHUAI , WU XIAO-QU , CHEN DE-CHAO , AO CHENG-CE , LI SHU-HONG
Published: March 2024

Lyophyllum lixivium sp. nov., collected from southwestern China, is described, illustrated, and discussed based on morphological characteristics and molecular data (ITS and nrLSU). Lyophyllum lixivium has umbonate to slightly depressed pileus, a cylindrical stipe that slightly enlarges towards the base, fuzz at the base, basidiospores mostly broadly ellipsoid, rarely fusiform lacrymoid or amygdaliform with an acute apex in side view, abundant clamp connections at the pileus surface and hymenophoral trama. Morphologically and phylogenetically similar species were compared with L. lixivium in this study.
Dutch secondary school counselors’ and tutors’ views on how students should make study profile choices
Authors: Wichgers Inge JM , Korpershoek Hanke , Warrens Matthijs J , Dijks Monique A , Bosker Roel J
Published: March 2024

Student counselors and tutors guide students’ choices of study profiles (subjects) within Dutch secondary education. This study addressed three research questions: (1) According to counselors and tutors, what factors should inform students’ study profile choices? (2) Into what types can the views of counselors and tutors be classified? (3) According to counselors and tutors, which factors should secondary school students consider when choosing their study profiles in a forced-choice situation? Interviews held with 70 tutors and counselors identified students’ interests, abilities, and future-oriented considerations as most important (RQ1). Six types of views were identified in which one, two, or all of the above-mentioned factors were regarded the most important by the participants (RQ2). Responses to the forced-choice situations largely confirmed different perspectives on the factors: the majority of participants perceived students’ interests very important (RQ3).
Human rights paradox: Explaining the undeportability of irregular Chinese migrants in the UK
Authors: Luo Siyu
Published: March 2024

Many migrants remain in host countries under a state of undeportability—a paradoxical circumstance in which they confront both an extreme unlikelihood of deportation and an imminent threat of it. Drawing on the case of irregular Chinese migrants in the UK, this article argues that the situation stems from what I term a ‘human rights paradox’—a contradiction between the universal human rights norms that mandate governments to protect the rights inherent to all human beings and the persistent state sovereignty and the growing anti-immigration sentiment that relegates non-citizens, particularly those having no legal status, to the margins of the human rights system. Hence, undeportability has its roots in the foundational principles of liberal democracy, rather than simply resulting from ineffective immigration policies or individual resistance to deportation.
Cross-border workers - navigating the challenges of social security coordination rules in the era of telework in the European Union
Authors: Aceto Fenicia
Published: March 2024

In 1 2020, there were 1.7 million cross-border workers in the European Union, creating difficulties in determining the applicable legislation for social security matters. The reason for this complexity is that even in cross-border activities, the legislation of only one Member State is applicable according to the Coordination Regulation 883/2004. This article examines the evolving landscape of social security coordination in the European Union. It explores the interplay between the European principle of free movement of workers and the complexities arising from various national social security systems, combined with the increase in telework. The article outlines the foundational legal frameworks underpinning social security within the European Union, including the Coordination Regulation EC 883/2004, and discusses primarily the challenges in applying these rules to cross-border teleworkers. It further analyses the implications of the new Multilateral Framework Agreement, providing a nuanced understanding of its role in offering simplified procedures and legal certainty for habitual cross-border teleworkers. The article also highlights the Agreement's limitations, including its restricted scope and the persisting administrative burdens. The discussion extends to the broader context of ongoing legislative efforts and the need for more flexible and modern social security coordination rules in the European Union. The article aims to shed light on the critical issues surrounding social security coordination in an era of evolving work practices.
The robot butler: How and why should we study predictive algorithms and artificial intelligence (AI) in healthcare?
Authors: Gjødsbøl Iben Mundbjerg , Ringgaard Anna Kirstine , Holm Peter Christoffer , Brunak Søren , Bundgaard Henning
Published: March 2024

Artificial intelligence (AI) and algorithms are heralded as significant solutions to the widening gap between the rising healthcare needs of ageing and multi-morbid populations and the scarcity of resources to provide such care.

Objective

This article investigates how the PMHnet algorithm – an AI prognostication tool developed in Denmark to predict the one-year all-cause mortality risk for patients hospitalized with ischemic heart disease – was presented to cardiologists working in the hospital setting, and how they responded to this novel decision-support tool.

Methods

Empirically, we draw upon ethnographic fieldwork in the Danish-led international research project, PM Heart, which since 2019 has developed the PMHnet algorithm and implemented the software into the electronic health record system in hospitals in Eastern Denmark (the Capital Region and Region Zealand).

Results

Paying careful attention to the hopes and concerns of cardiologists who will have to embrace and adapt to algorithmic tools in their everyday work of diagnosing and treating patients, we identify three analytical themes meriting attention when AI is implemented in healthcare: 1) the re-negotiation of agency and autonomy in human-algorithm relations, 2) accountability in algorithmic prognostication and 3) the complex relationship between association and causation actualized by predictive algorithms. From these analytical themes, we elicit methodological questions to guide future ethnographic explorations of how AI and advanced algorithms are put to use in the healthcare system, with what implications, and for whom.

Conclusion

We conclude that local, qualitative investigations of how algorithms are used, embraced and contested in everyday clinical practice are needed in order to understand their implications – good and bad, intended and unintended – for clinicians, patients and healthcare provision.
Prevention, Diagnosis, and Management of Intraoperative Spinal Cord Injury in the Setting of Spine Surgery: A Proposed Care Pathway
Authors: Srikandarajah Nisaharan , Hejrati Nader , Alvi Mohammed Ali , Quddusi Ayesha , Tetreault Lindsay A. , Evaniew Nathan , Skelly Andrea C. , Douglas Sam , Rahimi-Movaghar Vafa , Arnold Paul M , Kirshblum Steven , Kwon Brian K. , Fehlings Michael G.
Published: March 2024

Study Design

This study is a mixed methods approach.

Objectives

Intraoperative spinal cord injury (ISCI) is a challenging complication in spine surgery. Intra-operative neuromonitoring (IONM) has been developed to detect changes in neural function. We report on the first multidisciplinary, international effort through AO Spine and the Praxis Spinal Cord Institute to develop a comprehensive guideline and care pathway for the prevention, diagnosis, and management of ISCI.

Methods

Three literature reviews were registered on PROSPERO (CRD 42022298841) and performed according to PRISMA guidelines: (1) Definitions, frequency, and risk factors for ISCI, (2) Meta-analysis of the accuracy of IONM for diagnosis of ISCI, (3) Reported management approaches for ISCI and related events. The results were presented in a consensus session to decide the definition of IONM and recommendation of its use in high-risk cases. Based on a literature review of management strategies for ISCI, an intra-operative checklist and overall care pathway was developed by the study team.

Results

An operational definition and high-risk patient categories for ISCI were established. The reported incidence of deficits was documented to be higher in intramedullary tumour spine surgery. Multimodality IONM has a high sensitivity and specificity. A guideline recommendation of IONM to be employed for high-risk spine cases was made. The different sections of the intraoperative checklist include surgery, anaesthetic and neurophysiology. The care pathway includes steps (1) initial clinical assessment, (2) pre-operative planning, (3) surgical/anaesthetic planning, (4) intra-operative management, and (5) post-operative management.

Conclusions

This is the first evidence based comprehensive guideline and care pathway for ISCI using the GRADE methodology. This will facilitate a reduction in the incidence of ISCI and improved outcomes from this complication. We welcome the wide implementation and validation of these guidelines and care pathways in prospective, multicentre studies.
Perspectives of Canadian Healthcare and Harm Reduction Workers on Mobile Overdose Response Services: A Qualitative Study
Authors: Sedaghat Navid , Seo Boogyung , Rider Nathan , Rioux William , Ghosh S. Monty
Published: March 2024

Background:

Supervised consumption sites (SCS) are an evidence-based intervention proven effective for preventing drug overdose deaths. Obstacles to accessing SCS include stigma, limited hours of operation, concerns about policing, and limited geographic availability. Mobile overdose response services (MORS) are novel technologies that provide virtual supervised consumption to help reduce the risk of fatal overdoses, especially for those who use alone. MORS can take various forms, such as phone-based hotlines and mobile apps. The aim of this article is to assess the perceptions of MORS among healthcare and harm reduction staff to determine if they would be comfortable educating clients about these services.

Methods:

Twenty-two healthcare and harm reduction staff were recruited from Canada using convenience, snowball, and purposive sampling techniques to complete semistructured interviews. Inductive thematic analysis informed by grounded theory was used to identify main themes and subthemes.

Results:

Four themes were identified: (1) increasing MORS awareness among healthcare providers was seen as useful; (2) MORS might lessen the burden of drug overdoses on the healthcare system but could also increase ambulance callouts; (3) MORS would benefit from certain improvements such as providing harm reduction resources and other supports; and (4) MORS are viewed as supplements for harm reduction, but SCS were preferred.

Conclusions:

This research provides valuable perspectives from healthcare and harm reduction workers to understand their perception of MORS and identifies key areas of potential improvement. Practical initiatives to improve MORS implementation outcomes exist.
Exploring Genetic Diversity within aus Rice Germplasm: Insights into the Variations in Agro-morphological Traits
Authors: Sar Puranjoy , Gupta Sonal , Behera Motilal , Chakraborty Koushik , Ngangkham Umakanta , Verma Bibhash Chandra , Banerjee Amrita , Hanjagi Prashantkumar S. , Bhaduri Debarati , Shil Sandip , Kumar Jitendra , Mandal Nimai Prasad , Kole Paresh Chandra , Purugganan Michael D. , Roy Somnath
Published: March 2024

The aus (Oryza sativa L.) varietal group comprises of aus, boro, ashina and rayada seasonal and/or field ecotypes, and exhibits unique stress tolerance traits, making it valuable for rice breeding. Despite its importance, the agro-morphological diversity and genetic control of yield traits in aus rice remain poorly understood. To address this knowledge gap, we investigated the genetic structure of 181 aus accessions using 399,115 SNP markers and evaluated them for 11 morpho-agronomic traits. Through genome-wide association studies (GWAS), we aimed to identify key loci controlling yield and plant architectural traits.

Our population genetic analysis unveiled six subpopulations with strong geographical patterns. Subpopulation-specific differences were observed in most phenotypic traits. Principal component analysis (PCA) of agronomic traits showed that principal component 1 (PC1) was primarily associated with panicle traits, plant height, and heading date, while PC2 and PC3 were linked to primary grain yield traits. GWAS using PC1 identified OsSAC1 on Chromosome 7 as a significant gene influencing multiple agronomic traits. PC2-based GWAS highlighted the importance of OsGLT1 and OsPUP4/ Big Grain 3 in determining grain yield. Haplotype analysis of these genes in the 3,000 Rice Genome Panel revealed distinct genetic variations in aus rice.

In summary, this study offers valuable insights into the genetic structure and phenotypic diversity of aus rice accessions. We have identified significant loci associated with essential agronomic traits, with GLT1, PUP4, and SAC1 genes emerging as key players in yield determination.
Full-length 16S rRNA gene sequencing by PacBio improves taxonomic resolution in human microbiome samples
Authors: Buetas Elena , Jordán-López Marta , López-Roldán Andrés , D’Auria Giuseppe , Martínez-Priego Llucia , De Marco Griselda , Carda-Diéguez Miguel , Mira Alex
Published: March 2024

Background

Sequencing variable regions of the 16S rRNA gene (≃300 bp) with Illumina technology is commonly used to study the composition of human microbiota. Unfortunately, short reads are unable to differentiate between highly similar species. Considering that species from the same genus can be associated with health or disease it is important to identify them at the lowest possible taxonomic rank. Third-generation sequencing platforms such as PacBio SMRT, increase read lengths allowing to sequence the whole gene with the maximum taxonomic resolution. Despite its potential, full length 16S rRNA gene sequencing is not widely used yet. The aim of the current study was to compare the sequencing output and taxonomic annotation performance of the two approaches (Illumina short read sequencing and PacBio long read sequencing of 16S rRNA gene) in different human microbiome samples. DNA from saliva, oral biofilms (subgingival plaque) and faeces of 9 volunteers was isolated. Regions V3-V4 and V1-V9 were amplified and sequenced by Illumina Miseq and by PacBio Sequel II sequencers, respectively.

Results

With both platforms, a similar percentage of reads was assigned to the genus level (94.79% and 95.06% respectively) but with PacBio a higher proportion of reads were further assigned to the species level (55.23% vs 74.14%). Regarding overall bacterial composition, samples clustered by niche and not by sequencing platform. In addition, all genera with > 0.1% abundance were detected in both platforms for all types of samples. Although some genera such asStreptococcustended to be observed at higher frequency in PacBio than in Illumina (20.14% vs 14.12% in saliva, 10.63% vs 6.59% in subgingival plaque biofilm samples) none of the differences were statistically significant when correcting for multiple testing.

Conclusions

The results presented in the current manuscript suggest that samples sequenced using Illumina and PacBio are mostly comparable. Considering that PacBio reads were assigned at the species level with higher accuracy than Illumina, our data support the use of PacBio technology for future microbiome studies, although a higher cost is currently required to obtain an equivalent number of reads per sample.
Identification of potential cell death-related biomarkers for diagnosis and treatment of osteoporosis
Authors: Li Mingliang , Wang Xue , Guo Mingbo , Zhang Wenlong , Li Taotao , Zheng Jinyang
Published: March 2024

Background

This study aimed to identify potential biomarkers for the diagnosis and treatment of osteoporosis (OP).

Methods

Data sets were downloaded from the Gene Expression Omnibus database, and differentially programmed cell death-related genes were screened. Functional analyses were performed to predict the biological processes associated with these genes. Least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest (RF) machine learning algorithms were used to screen for characteristic genes, and receiver operating characteristics were used to evaluate the diagnosis of disease characteristic gene values. Gene set enrichment analysis (GSEA) and single-sample GSEA were conducted to analyze the correlation between characteristic genes and immune infiltrates. Cytoscape and the Drug Gene Interaction Database (DGIdb) were used to construct the mitochondrial RNA-mRNA-transcription factor network and explore small-molecule drugs. Reverse transcription real-time quantitative PCR (RT-qPCR) analysis was performed to evaluate the expression of biomarker genes in clinical samples.

Results

In total, 25 differential cell death genes were identified. Among these, two genes were screened using the LASSO, SVM, and RF algorithms as characteristic genes, including BRSK2 and VPS35. In GSE56815, the area under the receiver operating characteristic curve of BRSK2 was 0.761 and that of VPS35 was 0.789. In addition, immune cell infiltration analysis showed that BRSK2 positively correlated with CD56dim natural killer cells and negatively correlated with central memory CD4 + T cells. Based on the data from DGIdb, hesperadin was associated with BRSK2, and melagatran was associated with VPS35. BRSK2 and VPS35 were expectably upregulated in OP group compared with controls (all p < 0.05).

Conclusions

BRSK2 and VPS35 may be important diagnostic biomarkers of OP.
RETRACTED ARTICLE: Potential use of
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and prevention method
in viral infection
Authors: Muzammil Khursheed , Hooshiar Mohammad Hosseini , Varmazyar Shirin , Omar Thabit Moath , Karim Manal Morad , Aadi Sadeq , Kalavi Shaylan , Yasamineh Saman
Published: March 2024

Cellular lipid membranes serve as the primary barrier preventing viral
infection of the host cell and provide viruses with a critical initial point of
contact. Occasionally, viruses can utilize lipids as viral receptors. Viruses depend
significantly on lipid rafts for infection at virtually every stage of their life
cycle. The pivotal role that proprotein convertase subtilisin/kexin Type 9 (PCSK9)
plays in cholesterol homeostasis and atherosclerosis, primarily by
post-transcriptionally regulating hepatic low-density lipoprotein receptor (LDLR)
and promoting its lysosomal degradation, has garnered increasing interest.
Conversely, using therapeutic, fully humanized antibodies to block PCSK9 leads to a
significant reduction in high LDL cholesterol (LDL-C) levels. The Food and Drug
Administration (FDA) has approved PCSK9 inhibitors, including inclisiran
(Leqvio®), alirocumab (Praluent), and evolocumab (Repatha). At present,
active immunization strategies targeting PCSK9 present a compelling substitute for
passive immunization through the administration of antibodies. In addition to the
current inquiry into the potential therapeutic application of PCSK9 inhibition in
human immunodeficiency virus (HIV)-infected patients for hyperlipidemia associated
with HIV and antiretroviral therapy (ART), preclinical research suggests that PCSK9
may also play a role in inhibiting hepatitis C virus (HCV) replication. Furthermore,
PCSK9 inhibition has been suggested to protect against dengue virus (DENV)
potentially and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
viruses. Recent evidence regarding the impact of PCSK9 on a variety of viral
infections, including HCV, HIV, DENV, and SARS-CoV-2, is examined in this article.
As a result, PCSK9 inhibitors and vaccines may serve as viable host therapies for
viral infections, as our research indicates that PCSK9 is significantly involved in
the pathogenesis of viral infections.

Graphical abstract: the function of proprotein convertase subtilisin/kexin
type 9 (PCSK9) in reducing cholesterol uptake and low-density lipoprotein
receptor (LDLR) recycling in various viral infections, including hepatitis C
virus (HCV), human immunodeficiency viruses (HIV), dengue virus (DENV), rift
valley fever (RVF), and severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) is summarized in this figure
LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms
Authors: Liu He , Wei Xuemei , Wang Zhefen , Huang Xiaonan , Li Mengyang , Hu Zhen , Zhang Kexin , Hu Qiwen , Peng Huagang , Shang Weilong , Yang Yi , Wang Yuting , Lu Shuguang , Rao Xiancai
Published: March 2024

Background

Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established.

Results

In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300.

Conclusions

Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.
The upregulation of VGF enhances the progression of oral squamous carcinoma
Authors: Chou Chung-Hsien , Yen Chun-Han , Liu Chung-Ji , Tu Hsi-Feng , Lin Shu-Chun , Chang Kuo-Wei
Published: March 2024

Background

Oral squamous cell carcinoma (OSCC) is a prevalent neoplasm worldwide, necessitating a deeper understanding of its pathogenesis. VGF nerve growth factor inducible (VGF), a neuropeptide, plays critical roles in nerve and endocrine cell regulation.

Methods

In this study, the TCGA datasets were initially screened, identifying the upregulation of VGF in various malignancies. We focused on OSCC cell lines, identifying the suppressor mRNA miR-432-5p as a negative regulator of VGF. Additionally, we examined the prognostic value of VGF expression in OSCC tumors and its impact on cellular functions.

Results

VGF expression was found to be an independent prognostic predictor in OSCC tumors. Cells expressing VGF exhibited increased oncogenicity, influencing the proliferation and migration of oral mucosal fibroblast. Transcriptome analysis revealed associations between VGF and various pathological processes, including malignancies, exosome release, fibrosis, cell cycle disruption, and tumor immune suppression. Moreover, IL23R expression, a favorable OSCC prognostic factor, was inversely correlated with VGF expression. Exogenous IL23R expression was found to suppress VGF-associated mobility phenotypes.

Conclusions

This study highlights the multifaceted role of VGF in OSCC pathogenesis and introduces the miR-432-5p-VGF-IL23R regulatory axis as a critical mediator. The combined expression of VGF and IL23R emerges as a potent predictor of survival in oral carcinoma cases, suggesting potential implications for future therapeutic strategies.
Clinical efficiency of three-port inflatable robot-assisted thoracoscopic surgery in mediastinal tumor resection
Authors: Peng Hao , He YuanPeng , Sheng Siqi , Maitiyasen Maierhaba , Li Jingfeng , Liu Yvxuan , Chen Jing , Hou Xinyu , Song Haizhu , Yi Jun
Published: March 2024

Background

Aimed to assess clinical effect of three-port inflatable robot-assisted thoracoscopic surgery in mediastinal tumor resection by comparing results of the robot group with the video group.

Methods

Retrospectively analyze 179 patients diagnosed with anterior mediastinal tumor from May 2017 to August 2021. Two groups were divided according to the surgical approach, including 92 cases in the RATS group and 87 cases in the VATS group. The results were analyzed between two groups with variables of age, sex, BMI, tumor size, and diagnosis. Perioperative clinical data was gathered to compare.

Result

There were no significant differences between the 2 groups with regards to demographic data and clinical features. There were no significant differences inoperative time and duration of chest tube via RATS vs. VATS. The intraoperative blood loss was statistically significantly different among the RATS and VATS groups (75.9 ± 39.6 vs. 97.4 ± 35.8 ml p = 0.042). The postoperative stay of patients in RATS group were significantly shorter than that in VATS group (2.3 ± 1.0 vs. 3.4 ± 1.4 day p = 0.035),

Conclusion

Three-port inflatable robot-assisted thoracoscopic surgery for mediastinal tumor is feasible and reliable it is more advantageous, and it provides the surgeon with advice on treatment choice.
Endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease
Authors: Cui Siyuan , Chen Xin , Li Jiayu , Wang Wei , Meng Deqi , Zhu Shenglong , Shen Shiwei
Published: March 2024

Background

The incidence of diabetic kidney disease (DKD) continues to rapidly increase, with limited available treatment options. One of the hallmarks of DKD is persistent inflammation, but the underlying molecular mechanisms of early diabetic kidney injury remain poorly understood. C-X-C chemokine receptor 2 (CXCR2), plays an important role in the progression of inflammation-related vascular diseases and may bridge between glomerular endothelium and persistent inflammation in DKD.

Methods

Multiple methods were employed to assess the expression levels of CXCR2 and its ligands, as well as renal inflammatory response and endothelial glycocalyx shedding in patients with DKD. The effects of CXCR2 on glycocalyx shedding, and persistent renal inflammation was examined in a type 2 diabetic mouse model with Cxcr2 knockout specifically in endothelial cells (DKD-Cxcr2eCKO mice), as well as in glomerular endothelial cells (GECs), cultured in high glucose conditions.

Results

CXCR2 was associated with early renal decline in DKD patients, and endothelial-specific knockout of CXCR2 significantly improved renal function in DKD mice, reduced inflammatory cell infiltration, and simultaneously decreased the expression of proinflammatory factors and chemokines in renal tissue. In DKD conditions, glycocalyx shedding was suppressed in endothelial Cxcr2 knockout mice compared to Cxcr2L/L mice. Modulating CXCR2 expression also affected high glucose-induced inflammation and glycocalyx shedding in GECs. Mechanistically, CXCR2 deficiency inhibited the activation of NF-κB signaling, thereby regulating inflammation, restoring the endothelial glycocalyx, and alleviating DKD.

Conclusions

Taken together, under DKD conditions, activation of CXCR2 exacerbates inflammation through regulation of the NF-κB pathway, leading to endothelial glycocalyx shedding and deteriorating renal function. Endothelial CXCR2 deficiency has a protective role in inflammation and glycocalyx dysfunction, suggesting its potential as a promising therapeutic target for DKD treatment.
Transcriptome and open chromatin analysis reveals the process of myocardial cell development and key pathogenic target proteins in Long QT syndrome type 7
Authors: Chen Peipei , Long Junyu , Hua Tianrui , Zheng Zhifa , Xiao Ying , Chen Lianfeng , Yu Kang , Wu Wei , Zhang Shuyang
Published: March 2024

Objective

Long QT syndrome type 7 (Andersen–Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism.

Methods and results

We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs. The spontaneous pulsation rate of myocardial cells in the mutation group was significantly lower than that in the repair CRISPR group, the action potential duration was prolonged, and the Kir2.1 current of the inward rectifier potassium ion channel was decreased, which is consistent with the clinical symptoms of ATS patients. Only ZNF528, a chromatin-accessible TF related to pathogenicity, was continuously regulated beginning from the cardiac mesodermal precursor cell stage (day 4), and continued to be expressed at low levels, which was identified by WGCNA method and verified with ATAC-seq data in the mutation group. Subsequently, it indicated that seven pathways were downregulated (all p < 0.05) by used single sample Gene Set Enrichment Analysis to evaluate the overall regulation of potassium-related pathways enriched in the transcriptome and proteome of late mature CMs. Among them, the three pathways (GO: 0008076, GO: 1990573 and GO: 0030007) containing the mutated gene KCNJ2 is involved that are related to the whole process by which a potassium ion enters the cell via the inward rectifier potassium channel to exert its effect were inhibited. The other four pathways are related to regulation of the potassium transmembrane pathway and sodium:potassium exchange ATPase (p < 0.05). ZNF528 small interfering (si)-RNA was applied to hiPSC-derived cardiomyocytes for CRISPR group to explore changes in potassium ion currents and growth and development related target protein levels that affect disease phenotype. Three consistently downregulated proteins (KCNJ2, CTTN and ATP1B1) associated with pathogenicity were verificated through correlation and intersection analysis.

Conclusion

This study uncovers TFs and target proteins related to electrophysiology and developmental pathogenicity in ATS myocardial cells, obtaining novel targets for potential therapeutic candidate development that does not rely on gene editing.

Graphical Abstract
Where should “Humans” be in “One Health”? Lessons from COVID-19 for One Health
Authors: Su Zhaohui , McDonnell Dean , Cheshmehzangi Ali , Bentley Barry L. , Šegalo Sabina , da Veiga Claudimar Pereira , Xiang Yu-Tao
Published: March 2024

The culling of animals that are infected, or suspected to be infected, with COVID-19 has fuelled outcry. What might have contributed to the ongoing debates and discussions about animal rights protection amid global health crises is the lack of a unified understanding and internationally agreed-upon definition of “One Health”. The term One Health is often utilised to describe the imperative to protect the health of humans, animals, and plants, along with the overarching ecosystem in an increasingly connected and globalized world. However, to date, there is a dearth of research on how to balance public health decisions that could impact all key stakeholders under the umbrella of One Health, particularly in contexts where human suffering has been immense. To shed light on the issue, this paper discusses whether One Health means “human-centred connected health” in a largely human-dominated planet, particularly amid crises like COVID-19. The insights of this study could help policymakers make more informed decisions that could effectively and efficiently protect human health while balancing the health and well-being of the rest of the inhabitants of our shared planet Earth.
Recovery pattern after decompression of central lumbar spinal stenosis: a prospective observational cohort study
Authors: Hareni Niyaz , Ebrahimnia Soheil , Rosengren Björn E. , Karlsson Magnus K.
Published: March 2024

Background

Detailed preoperative information is associated with superior outcomes. We aimed to describe the recovery pattern after decompression of central lumbar spinal stenosis (CLSS).

Methods

50 patients aged 51–85 years who underwent decompression without fusion due to CLSS were followed from before to after surgery (post-op day 1, 7, and 14). Back and leg pain were evaluated using the Numeric Rating Scale (NRS; 0 = no pain 0, 10 = worst pain) and quality of life using the EuroQol-5D index (0 = death, 1 = best), and EQ-5D-visual analogue scale (VAS; 0 = worst, 100 = best).

Results

NRS leg pain was reduced from preoperative to first postoperative day by 5.2 (6.1, 4.3) (mean (95%CI)], and NRS back pain from postoperative day 1–7 by 0.6 (1.2, 0.03) and from day 7 to 14 by 0.7 (1.3, 0.2)]. In contrast, EQ-5D index increased from preoperative to first postoperative day by 0.09 (0.06, 0.13) and from day 1 to 7 by 0.05 (0.02,0.08), and EQ-5D VAS from preoperative to first postoperative day by 13.7 (9.1, 18.3) and from day 1 to 7 by 6.0 (2.0, 10.0). After two weeks, 51% of the patients had improved above the minimal clinically important difference (MCID) in back pain and 71% in leg pain.

Conclusions

Patients scheduled for decompression due to CLSS should be informed that improvement in leg pain and quality of life in general can be expected within one day of surgery, that quality of life improves a little further in the first postoperative week, and that back pain improves in the first 2 postoperative weeks. In most patients, decompression without fusion due to CLSS seems to achieve clinically relevant improvement within 2 weeks.
Cordyceps sinensis relieves non-small cell lung cancer by inhibiting the MAPK pathway
Authors: Lu Tianming , Zhou Lirun , Chu Zheng , Song Yang , Wang Qixin , Zhao Minghong , Dai Chuanhao , Chen Lin , Cheng Guangqing , Wang Jigang , Guo Qiuyan
Published: March 2024

Objective

To determine the pharmacodynamic mechanism underlying Cordyceps sinensis relief in a murine model of non-small cell lung cancer (NSCLC).

Methods

We created a murine model of NSCLC and studied the potential molecular mechanism by which C. sinensis relieved NSCLC using a combination of transcriptomics, proteomics, and experimental validation.

Results

C. sinensis markedly suppressed the fluorescence values in mice with NSCLC, improved the pathologic morphology of lung tissue, ameliorated inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10, and the oxidative stress indicators superoxide dismutase, malondialdehyde, and glutathione peroxidase). Transcriptomics results showed that the therapeutic effect of C. sinensis was primarily involved in the differentiation and activation of T cells. Based on the proteomic results, C. sinensis likely exerted a protective effect by recruiting immune cells and suppressing tumor cell proliferation via the MAPK pathway. Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function.

Conclusions

Based on our preclinical study, C. sinensis was shown to exert a protective effect on NSCLC, primarily by inhibiting the MAPK pathway.
Formononetin reverses Treg/Th17 imbalance in immune-mediated bone marrow failure mice by regulating the PI3K/Akt signaling pathway
Authors: Lan Huixuan , Qiu Wei , Wu Jie , Hu Zhijing , Zhang Xiaomin , Zhu Lingling
Published: March 2024

Background

Severe aplastic anemia (SAA) is a syndrome of bone marrow failure which is life-threatening. Recent studies have demonstrated that CD4 + T cell subsets, including T regulatory (Treg) and T helper 17 (Th17) cells, play a pivotal role in the pathogenesis of SAA. Formononetin (FMN) is a natural compound extracted from the traditional Chinese medicine Huangqi, which has the ability to regulate the imbalance of Treg/Th17 cells in some inflammatory diseases. Nevertheless, the therapeutic effect of FMN in SAA has yet to be definitively established. Therefore, the objective of this research was to investigate the effect of FMN on SAA and elucidate its underlying mechanism.

Methods

In vivo experiments, the mice were divided into the following five groups: control, model, low-dose FMN, high-dose FMN, and positive control cyclosporine A group. The immune-mediated bone marrow failure (BMF) mouse model was established by the total body X-ray radiation and lymphocyte infusion. After 10 days of continuous administration of FMN, the numbers of Treg/Th17 cells in the bone marrow and spleen were assessed by flow cytometry. The protein expressions of PI3K/Akt pathway in the bone marrow and spleen was assessed by immunohistochemistry and western blotting. In vitro, the impact of FMN on the differentiation of naive CD4 + T cells into Treg cells was investigated by flow cytometry and ELISA.

Results

In comparison with the control group, the model group showed a reduction in bone marrow nucleated cells, a significant decrease in peripheral blood cells, and an altered CD8 + /CD4 + T cell ratio. These findings indicate the successful establishment of a mouse model of immune-mediated BMF. After FMN treatment, there were the increased levels of red blood cells and hemoglobin. In addition, FMN mitigated the bone marrow destruction and restored the CD8 + /CD4 + T cell ratio. Furthermore, in comparison with the control group, the model group showed the decreased levels of Treg cells and the increased levels of Th17 cells. After FMN treatment, there was a significantly increased number of Treg cells and a decreased number of Th17 cells. Additionally, FMN remarkably down-regulated the expression levels of PI3K and Akt proteins in immune-mediated BMF mice.

Conclusions

FMN alleviates immune-mediated BMF by modulating the balance of Treg/Th17 cells through the PI3K/Akt signaling pathway.
CT-based radiomics combined with hematologic parameters for survival prediction in locally advanced esophageal cancer patients receiving definitive chemoradiotherapy
Authors: Cui Jinfeng , Zhang Dexian , Gao Yongsheng , Duan Jinghao , Wang Lulu , Li Li , Yuan Shuanghu
Published: March 2024

Objectives

The purpose of this study was to investigate the prognostic significance of radiomics in conjunction with hematological parameters in relation to the overall survival (OS) of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy (dCRT).

Methods

In this retrospective analysis, a total of 122 patients with locally advanced ESCC were included. These patients were randomly assigned to either the training cohort (n = 85) or the validation cohort (n = 37). In the training group, the least absolute shrinkage and selection operator (LASSO) regression was utilized to choose the best radiomic features for calculating the Rad-score. To develop a nomogram model, both univariate and multivariate analyses were conducted to identify the clinical factors and hematologic parameters that could predict the OS. The performance of the predictive model was evaluated using the C-index, while the accuracy was assessed through the calibration curve.

Results

The Rad-score was calculated by selecting 10 radiomic features through LASSO regression. OS was predicted independently by neutrophil-to-monocyte ratio (NMR) and Rad-score according to the results of multivariate analysis. Patients who had a Rad-score > 0.47 and an NMR > 9.76 were at a significant risk of mortality. A nomogram was constructed using the findings from the multivariate analysis. In the training cohort, the nomogram had a C-index of 0.619, while in the validation cohort, it was 0.573. The model’s accuracy was demonstrated by the calibration curve, which was excellent.

Conclusion

A prognostic model utilizing radiomics and hematologic parameters was developed, enabling the prediction of OS in patients with ESCC following dCRT.

Critical relevance statement

Patients with esophageal cancer who underwent definitive chemoradiotherapy may benefit from including CT radiomics in the nomogram model.

Key points

• Predicting the prognosis of ESCC patients before treatment is particularly important.

• Patients with a Rad-score > 0.47 and neutrophil-to-monocyte ratio > 9.76 had a high risk of mortality.

• CT-based radiomics nomogram model could be used to predict the survival of patients.

Graphical Abstract
Gradient estimates for a class of elliptic equations with logarithmic terms
Authors: Gao Ze , Guo Qiming
Published: March 2024

We obtain the gradient estimates of the positive solutions to a nonlinear elliptic equation on an n-dimensional complete Riemannian manifold $(M, g)$
(
M
,
g
)
$$ \Delta u +au(\ln{u})^{p}+bu\ln{u}=0, $$
Δ
u
+
a
u

(
ln
u
)

p

+
b
u
ln
u
=
0
,
where $a\ne 0$
a
≠
0
, b are two constants and $p=\frac{k_{1}}{2k_{2}+1}\ge 2$
p
=

k
1

2

k
2

+
1

≥
2
, here $k_{1}$

k
1

and $k_{2}$

k
2

are two positive integers. The gradient bound is independent of the bounds of the solution and the Laplacian of the distance function. As the applications of the estimates, we show the Harnack inequality and the upper bound of the solution.
Murraya koenigii (L.) Sprengel seeds and pericarps in relation to their chemical profiles: new approach for multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia
Authors: El-Shiekh Riham A. , Elshimy Rana , Mandour Asmaa A. , Kassem Hanaa A. H. , Khaleel Amal E. , Alseekh Saleh , Fernie Alisdair R. , Salem Mohamed A.
Published: March 2024

Acinetobacterbaumannii is without a doubt one of the most problematic bacteria causing hospital-acquired nosocomial infections in today's healthcare system. To solve the high prevalence of multi-drug resistant (MDR) in A.baumannii, we investigated one of the medicinal plants traditionally used as antibacterial agent; namely Murrayakoenigii (L.) Sprengel. The total methanolic extracts of seeds and pericarps were prepared and their anti-bacterial activity was assessed using the agar diffusion method and minimum inhibitory concentration (MIC) was then calculated as compared to tigecycline. Then, an in-vivo murine model was established which confirmed the promising activity of M.koenigii seeds in demonstrating anti-bacterial and anti-inflammatory actions. The histopathological study of lungs, scoring of pulmonary lesions, counting of bacterial loads after infection by multi-drug resistant A.baumannii all provided evidence to support these findings. LC–MS/MS profiling coupled to molecular networking and chemometrics detected the presence of carbazole alkaloids, and coumarins as dominate metabolites of the active seed extracts. Positively correlated metabolites to antibacterial potential were 6-(2ʹ,3ʹ-dihydroxy-3-methylbutyl)-8-prenylumbelliferone, scopoline, and 5-methoxymurrayatin. An in-silico study was also performed on the crystal structure of MurF from A.baumannii (PDB ID: 4QF5), the studied structures of the mentioned extracts revealed good docking interaction at the active site suggestive of competition with the ATP ligand. These collective findings suggest that extracts of Murrayakoenigii (L.) Sprengel seed is a novel prospective for the discovery of drug candidates against infections caused by MDR A.baumannii.
Value evaluation model (VEM) of ancient Chinese military settlement heritage: a case study of Liaoxi Corridor in the Ming Dynasty
Authors: Fan Xixuan , Wang Zhen , Li Shifen
Published: March 2024

The Ming Great Wall Military Defense System is the most complete ancient military cultural heritage in China, which is of great significance to the study of China’s ancient military defense mechanism and pattern. Military settlement is an important carrier of this mechanism. The estimation and in-depth understanding of its value can further excavate the profound connotation of the military defense system and the Great Wall spatial pattern in the Ming Dynasty. This paper adopts the AHP-CRITIC weighting approach to determine the weights of the historical value, scientific value, social value, cultural value and artistic value of the settlement heritage, so as to construct the value evaluation model of military settlements, and takes 34 Ming Great Wall military settlements in the Liaoxi Corridor as an example for evaluation. The results of the evaluation identified the priority settlements for conservation and development, and also explored their relationship with historical status, urbanization processes and official policies. The evaluation model constructed in this paper has a certain universality, and can also be followed in the evaluation of other military settlements in the Ming Great Wall Defense System, so as to obtain the overall cognition of the settlement system.