bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between peripheral venous catheter failure and care complexity factors in emergency department: a cross-sectional study
Authors: Urbina Andrea , Juvé-Udina Maria-Eulàlia , Adamuz Jordi , González-Samartino Maribel , Jiménez-Martínez Emilio , Delgado-Hito Pilar , Romero-García Marta
Published: October 2024

Objective

The objective was to determine the prevalence of peripheral venous catheter (PVC) failure and its association with care complexity individual factors (CCIFs) in emergency department (ED) patients.

Design

A cross-sectional, descriptive-correlational study was performed.

Methods

All patients with a PVC inserted in the ED of a tertiary hospital were included. The period of study was from June 2021 to June 2022. The main outcomes were PVC failure (phlebitis, extravasation/infiltration, dysfunction/occlusion and dislodgement/involuntary withdrawal) and 26 CCIFs categorised into 5 domains (psycho-emotional, mental-cognitive, sociocultural, developmental and comorbidity/complications). Other secondary variables were also collected, such as level of triage or nursing care plan. All data were collected retrospectively from the electronic health records. A descriptive and inferential analysis was performed.

Results

A total of 35 968 patients with one or more PVC inserted during their ED visit were included in the study. The prevalence of PVC failure was 0.9% (n=316). The statistically significant CCIFs associated with PVC failure were: incontinence, haemodynamic instability, transmissible infection, vascular fragility, anxiety and fear, impaired adaptation, consciousness disorders, lack of caregiver support and agitation. In addition, we identified that patients with a higher number of CCIFs were more frequently experienced PVC failure.

Conclusion

This study identified a prevalence of PVC failure in the ED of around 1%. The most prevalent complication was dysfunction, followed by extravasation and dislodgement. In addition, PVC failure was associated with comorbidity/complications, psycho-emotional and mental-cognitive CCIFs domains.
Correlation of programmed death-ligand 1 expression in tumour cells between diagnostic small biopsies performed by radial EBUS and surgical specimens of peripheral lung cancer
Authors: Lachkar Samy , Gervereau Diane , Loïc Perrot , De Marchi Marielle , Morisse Helene , Dantoing Edouard , Piton Nicolas , Thiberville Luc , Salaün Mathieu , Guisier Florian
Published: October 2024

Background and objective

Expression of programmed death-ligand 1 (PD-L1) in tumour cells (TCs) is predictive of immunotherapy efficacy in non-small cell lung cancer (NSCLC). Small biopsy samples collected by bronchoscopy are often used to diagnose peripheral lung cancer. It is questionable whether these small samples from radial endobronchial ultrasonography (r-EBUS) procedures are representative of PD-L1 expression in TCs.

Methods

We retrieved data of consecutive patients who had surgery for NSCLC and previous r-EBUS biopsy sampling, from 2017 to 2019 in our centre. PD-L1 expression in tumour cells was categorised as <1%, 1%–49% and ≥50%. PD-L1 expression was compared between r-EBUS samples and surgical specimens.

Results

Among 1026 patients who had r-EBUS, 521 had a diagnosis of lung cancer on r-EBUS sample. PD-L1 testing was indicated in 356 cases and results were considered contributive in 325 cases (91%). 82 patients with PD-L1 expression in r-EBUS samples had subsequent surgical resection of the nodule and were included in the study. PD-L1 expression was identical between r-EBUS samples and surgical specimens in 67% of cases, with kappa 0.44 (p<0.001). 82% of patients with PD-L1≥50% in surgical specimens were identified in r-EBUS samples. Nonetheless, 31% of patients with no PD-L1 expression in r-EBUS samples had some expression in surgical specimens.

Conclusion

Small samples obtained by r-EBUS are adequate for assessment of PD-L1 expression in tumour cells, with moderate concordance compared to surgical specimens. Reassessment of PD-L1 expression in larger samples may be useful to guide therapy in patients with no PD-L1 expression in r-EBUS samples.
Influence of procedural timing on the preventive yield of percutaneous patent foramen ovale closure
Authors: Jerónimo Adrián , Nombela-Franco Luis , Simal Patricia , Freixa Xavier , Cerrato Enrico , Cruz-Gonzalez Ignacio , Dueñas Guillermo , Veiga-Fernandez Gabriela , Goncalves-Ramirez Luis Renier , Garcia-Blas Sergio , Fernández-Revuelta Ana , Cepas-Guillén Pedro , Tomassini Francesco , Lopez-Tejero Sergio , Gonzalez-Manzanares Rafael , De la Torre Hernandez Jose M , Perez de Prado Armando , Valero Ernesto , Gabani Rami , Travieso Alejandro , de Agustín Jose Alberto , Tirado Gabriela , Jimenez-Quevedo Pilar , Salinas Pablo
Published: October 2024

Background

The benefit of patent foramen ovale closure (PFOC) ≤9 months after a cryptogenic stroke has been demonstrated in several randomised clinical trials. There is, however, insufficient data to support PFOC in non-recent cryptogenic strokes.

Aims

The objective of the study was to evaluate the effectiveness of PFOC in relation to the time since the patient’s most recent cryptogenic cerebrovascular event (CVE) or systemic embolism (SE).

Methods

We conducted a multicentre, retrospective cohort study with international participation, to assess the results of an early closure (EC, <9 months) for secondary prevention versus a delayed closure (DC, ≥9 months). Recurrence of CVE/SE following PFOC was evaluated as the primary endpoint.

Results

496 patients were included (65% in the EC and 35% in the DC group). With the exception of a larger defect size in the DC group (tunnel width 6 (4–14) vs 12 (6–16) mm, p=0.005), similar clinical and echocardiographic baseline features were observed between the groups. No differences were observed regarding the type of devices used for PFOC, procedural success rate (99.4 in EC vs 98.8% DC group) and periprocedural complications (2.1% vs 0.8%). Median follow-up was 2.0 (1.2–4.2) years in the whole study population. Recurrence of CVE/SE (3.9% vs 2.6%, p=0.443), death (1.4% vs 1.0%, p=0.697), residual shunt 12 months after PFOC, or antithrombotic treatment strategy were comparable in both groups during follow-up. A subanalysis comparing very delayed PFOC (≥24 months) also showed no differences in recurrence (4.2% in the <24-month vs 3.4% in the ≥24-month group, p=0.770).

Conclusion

Patients undergoing PFOC before and after 9 months after the index event had a comparable recurrence rate of CVE/SE. These findings suggest that PFOC might be recommended in cryptogenic CVE/SE which are more remote than 9 months.
Investigating the optical bistability of pure spheroidal nanoinclusions in passive and active host matrices
Authors: Getachew Shewa , Berga Girma
Published: October 2024

The study examined the effects of the depolarization factor ( L) and the real and imaginary parts of the dielectric function of the host matrix (εh) on the local field enhancement factor and optical bistability of pure spheroidal nanoinclusions with both passive and active host matrices. By solving the Laplace equation in the quasi-static limit, we derived expressions for the electric potentials of the pure spheroidal nanoinclusions. We then incorporated L and the Lorentz–Drude model into these expressions to derive the equation for the enhancement factor in the core of the spheroidal nanoinclusions. The results show that, regardless of whether L varies or remains constant, the pure spheroidal nanoinclusions exhibit only one set of enhancement factor peaks, independent of whether the host matrix is passive or active. However, for the same increase in εh, the enhancement factor intensities of the pure metal spheroidal nanoinclusions are higher when the host matrix is active compared to when it is passive. The number and intensities of the enhancement factor peaks, as well as the optical bistability of the pure spheroidal nanoinclusions, vary significantly depending on whether the core is made of a passive or active dielectric material. Furthermore, by adjusting parameters such as L and the real and imaginary parts of the host matrices, we were able to achieve tunable enhancement factors and optical bistability, which could be useful for applications in optical sensing, nonlinear optics, and quantum optics.
Equilibria and the protomodel of the Sun’s atmosphere by Karl Schwarzschild in hindsight
Authors: Koza Július
Published: October 2024

The concepts of radiative and adiabatic equilibria, introduced by Karl Schwarzschild in his seminal paper Ueber das Gleichgewicht der Sonnenatmosphäre published in January 1906, are the founding blocks of the theory of radiative transfer, stellar structure, and solar physics. Careful reading of the paper and its later English translation reveals small formal inaccuracies and ambiguities but with no consequences whatsoever for the final outcomes and conclusions. This paper offers their adjustments with respective derivations using contemporary formalism and sets Schwarzschild’s paper in context with a historical and modern perspective. Particular attention is paid to Schwarzschild’s largely forgotten limb-darkening formula for adiabatic equilibrium. The paper also reproduces Schwarzschild’s radiative equilibrium protomodel of the Sun’s atmosphere in graphical form and compares it with modern models presented in some of the most cited papers in stellar and solar physics.
Bifurcation analysis of Van der Pol–Mathieu equation for the dust grain charge with regularized (κ)-distributed electron-ion
Authors: Shahein R. A. , Al-Raddadi A. A.
Published: October 2024

This paper presents a novel viewpoint on nonlinear dust-acoustic waves (DAWs) in an unmagnetized collisionless plasma containing regularized [Formula: see text] distributed electrons and ions (ei) and negative dust grain. The nonlinear oscillatory system based on hybridization of the Van der Pol–Mathieu equation (VdPME) is derived by a new technique. By bifurcation analysis of the planar dynamical system (DS), the effects of parameters with the assistance of phase planes and time series of VdPME are studied. After analyzing the equation to identify the resonance region, a fourth-order Runge–Kutta method is used to solve it numerically. We explained the behavior of DA periodic, stable limit cycle, and chaotic limit cycle wave solutions with different parameters. These types of numerical solutions are illustrated in two-dimensional and three-dimensional graphics by changing the rate at which charged dust grain is produced [Formula: see text], as well as waste [Formula: see text] and comparing the results with those of earlier research. A novel bifurcation analysis of VdPE and VdPME is obtained with the effects of the cut-off factor [Formula: see text] of regularized [Formula: see text]-distribution (RKD) distributed ei, the superthermality of ei particles [Formula: see text], the ratio of ion to electron temperature [Formula: see text], and the ratio of dust to electron density [Formula: see text] illustrated.  It is noticed that the DAW shows promotion in width and amplitude as the frequency [Formula: see text] increases and it becomes rarefaction as the cut-off parameter [Formula: see text] increases. On the contrary, it becomes compressive under the impact of superthermality [Formula: see text] and [Formula: see text]. The obtained conclusions may help explain and comprehend a variety of applications in experimental plasma containing highly energy regularized [Formula: see text] dispersed ei, as well as in the interstellar medium.
Regional variations in cingulate cortex glutamate levels: a magnetic resonance spectroscopy study at 3 T
Authors: Choles Cassandra M. , Archibald Jessica , Ortiz Oscar , MacMillan Erin L. , Zölch Niklaus , Kramer John L. K.
Published: October 2024

In a large, sex-balanced sample of healthy individuals, we demonstrate that average regional differences (rostral to caudal) in cingulate cortex glutamate exist, using optimized experimental conditions and 3 T magnetic resonance spectroscopy techniques. Results align with observations from 7 T. A novel clustering approach was introduced to determine the number of patterns for glutamate in the healthy adult brain for the first time. These findings demonstrate that regional differences are detectable at 3 T when present and suggest the occurrence of multiple glutamate metabolism patterns in the cingulate.
Synaptic dynamics linked to widespread elevation of H-reflex before peripheral denervation in amyotrophic lateral sclerosis
Authors: Sangari Sina , Lackmy-Vallee Alexandra , Preuilh Arnaud , Peyre Iseline , Pradat Pierre-François , Marchand-Pauvert Véronique
Published: October 2024

Without significant evidence of peripheral denervation, H-reflex enhancement appears to be a widespread phenomenon, regardless of disease onset site. This increase is likely associated with a decrease in inhibitory control over presynaptic transmission of the synapse between muscle group Ia afferents and motoneurons. Although the link to exaggerated osteotendinous reflexes and spasticity implies a restricted role in identifying a pyramidal syndrome, its quantitative aspect positions the H-reflex as a valuable biomarker in clinical trials.
Prevalence of Extended‐Spectrum Beta‐Lactamase (ESBL)–Producing Escherichia coli in Humans, Food, and Environment in Kathmandu, Nepal: Findings From ESBL E. coli Tricycle Project
Authors: Acharya Jyoti , Jha Runa , Gompo Tulsi Ram , Chapagain Sharmila , Shrestha Lilee , Rijal Nisha , Shrestha Anjana , Koirala Pragya , Subedi Suraj , Tamang Binita , Kattel Hari Prasad , Khaniya Bishal , Shrestha Basudha , Karki Aruna , Adhikari Ram Prasad , Kayastha Sanita , Pradhan Prasil , Shrestha Sarada Duwal , Raghubanshi Bijendra Raj , Tuladhar Heera , Kansakar Palpasa , Shrestha Saugat , Shrestha Priyanka , Shrestha Binay , Soares Magalhaes Ricardo J. , Kakkar Manish , Govindakarnavar Arunkumar , Gocotano Allison , Samuel Reuben
Published: October 2024

The need to address antimicrobial resistance (AMR) through a One Health (OH) approach is now well recognized. There is, however, limited guidance on how AMR surveillance should be implemented across sectors to generate meaningful AMR and AMU data for decision‐making. Using a sympatric approach to cross‐sector sample collection, Nepal adopted the WHO extended‐spectrum beta‐lactamase (ESBL)–producing Escherichia coli (E. coli) Tricycle Project as a step toward OH surveillance for assessing the prevalence of ESBL‐producing E. coli across human, veterinary, and environment sectors. This involved a three‐stage approach: identification of human hotspots (Stage 1) and sample collection sites for poultry (Stage 2) and wastewater (Stage 3). A total of 53 blood cultures from patients with bloodstream infections (BSIs), 100 stool samples from healthy pregnant women, 220 poultry ceca from slaughterhouses and live markets, and 48 wastewater samples were processed for bacterial culture and analyzed for the presence of ESBL‐producing E. coli. The prevalence of ESBL‐producing E. coli among isolated E. coli was the highest in wastewater samples (91%) followed by human BSIs (49%), poultry (38.6%), and fecal carriage isolates from healthy pregnant females (15%). A statistically significant association was seen in the prevalence of multidrug resistance among ESBL producers (52%) and nonproducers (26%). ESBL‐producing E. coli was detected in all wastewater samples tested except for the upstream river. The findings of the study showed a high prevalence of ESBL‐producing E. coli in samples from all three sectors and provided baseline data based upon which strategies for the safe disposal of communal and hospital waste, integrated AMR surveillance, and control strategies could be planned and implemented.
Cardiac Metabolic Stress During Ischemia and Reperfusion in Patients Undergoing Coronary Artery Bypass Surgery Using Either Calafiore or Modified Del Nido Cardioplegic Solutions
Authors: Massa Abd Alhade , Izzat Ahmad Walid , Saadoun Rakan , Izzat Mohammad Bashar
Published: October 2024

Objective: Calafiore and modified del Nido cardioplegic solutions are currently being used during coronary artery bypass surgery. This study aims to compare myocardial ischemic stress associated with both solutions by studying the changes in cardiac metabolites during cardioplegic ischemic arrest and early reperfusion.

Methods: Biopsy specimens were taken from the left ventricles of 20 patients undergoing routine coronary artery bypass grafting using Calafiore or modified del Nido cardioplegic solutions. Biopsies were taken immediately after the beginning of extracorporeal circulation (basal biopsy), 30 min after application of the aortic cross‐clamp (ischemic biopsy), and 20 min following the removal of aortic cross‐clamp (reperfusion biopsy) and were analyzed for their amino acid and lactic acid contents using amino acid analyzer and appropriate kits. Peripheral blood samples were also collected for the determination of blood concentrations of cardiac proteins (CK‐MB and troponin I) using an immunofluorescence scanner.

Results: Both CK‐MB and troponin I increased significantly 12 h postoperatively and were associated with an increase in myocardial lactic acid, but there were no significant differences in markers of myocardial injury between the two groups. Comparison of amino acid concentrations between the two groups according to sampling time showed that glutamic acid concentrations were significantly lower in the Calafiore cardioplegia group compared to the del Nido cardioplegia group, but there were no other significant differences in markers of metabolic stress (taurine and alanine/glutamate ratio) between the two groups. Moreover, there were no significant differences in changes in amino acid concentrations regardless of the type of cardioplegic solution used.

Conclusions: Cardioplegic ischemic arrest and early reperfusion are associated with a rise in myocardial metabolic stress. Both Calafiore and modified del Nido cardioplegic solutions are effective in attenuating myocardial substrate derangements and confer equal myocardial protection during routine coronary artery bypass surgery.

Trial Registration: ClinicalTrials.gov identifier: NCT06287372
Development and Balance Evaluation for Land Use and Transport Interaction Using Node‐Place Model and Data Envelopment Analysis
Authors: Ma Xiaoyi , He Hongjie , Liu Mingmin , Jin An
Published: October 2024

To meet the evolving demands of land use and transport interaction (LUTI) assessment within China’s national territory spatial planning (NTSP) system, this paper introduces the level of development (LoD) and the level of matching (LoM) evaluation models, based on the traffic facility and land use factors. The LoD model, founded on the modified node‐place model, provides a comprehensive assessment of the traffic facility and land use development scales. Conversely, the LoM model, grounded in data envelopment analysis methods, evaluates the relative relationship between transport services and the travel demand generated by land use. The integrated use of LoD and LoM can both reflect the development scale and matching status between traffic services and travel activities, which are crucial contents in the planning works, especially within the NTSP framework. The proposed models are tested in the city of Guangzhou, and the LoD values exhibit peaks in central urban zones, suburban towns, and areas adjacent to railway transit, with a decline observed in rural farmland and ecological regions. In contrast, the LoM distribution performs a distinct pattern, highlighting numerous underperforming areas with congestion or idle problems in urban centers, alongside well‐coordinated regions showcasing a balance between traffic facilities and land uses in rural regions. Furthermore, the LoM scores revealed frequent instances of facility crowding in urban regions and intensive occurrences of facility idleness in rural areas. By marking regions with low LoD scores, the LoD model finds suitable application in determining the urban development border, essential for restricting land development and preserving farmland and ecological areas. Meanwhile, LoM aids in improving urban renewal efforts by assessing and optimizing the balance between intensive land uses and limited traffic facilities. Validated against the existing metrics, the combined use of LoD and LoM efficiently captures the most details of the LUTI process at the lowest computational cost.
Impact of COVID‐19 on the Participation of Iranian Adolescents in Daily Life: Development and Validation of the IAPAT‐C Tool
Authors: Joveini Ghodsiyeh , Lajevardi Laleh , Khalafbeigi Mitra , Hasani Mehraban Afsoon , Zareiyan Armin
Published: October 2024

Background and Purpose: The present study is aimed at evaluating the effects of the COVID‐19 pandemic on Iranian adolescents’ participation in various domains of life. The electronic version of the Iranian Adolescent Participation Assessment Tool‐COVID‐19 (IAPAT‐C) was developed and validated for this purpose.

Methods: This study was conducted in two phases. In the first phase, the electronic version of the IAPAT‐C was developed and validated through a methodological study involving five stages: content validity review, cognitive interviews, item analysis, structural validity assessment using confirmatory factor analysis, and reliability analysis. The tool was adapted from the previously validated IAPAT and revalidated for this study. In the second phase, the effects of COVID‐19 on adolescents’ participation were evaluated using a longitudinal one group before and after comparative design. The study involved 654 adolescents aged 13–18, and the data were analyzed using SPSS19 and G ∗Power 3 software.

Results: The IAPAT‐C evaluates the participation of Iranian adolescents in 54 daily life activities before and after the COVID‐19 pandemic. It utilizes a 5‐point Likert scale and was validated through an expert panel review for content validity. Additionally, cognitive interviews with six adolescents confirmed its comprehensibility, relevance, and comprehensiveness. Item analysis, based on data from 38 participants, demonstrated strong interitem correlations (0.6–0.94) and excellent internal consistency (Cronbach’s alpha > 0.7). The tool’s structural validity was supported by confirmatory factor analysis, which showed that the measurement model was a good fit. Convergent and discriminant validity of model constructs were also confirmed. Notably, COVID‐19 significantly impacted all aspects of adolescents’ lives, except for work.

Conclusion: The electronic version of the IAPAT‐C was valid and reliable. COVID‐19 significantly affected various aspects of Iranian adolescents’ daily lives. Accordingly, it is necessary to provide appropriate interventions and policies for this sensitive class.
Sellar Schwannoma Masquerading as Giant Pituitary Adenoma: A Diagnostic Challenge
Authors: Alkhaibary Ali , Alotaibi Norah Mohammad , Albattah Ghaida Abdullah , Alotaibi Rahaf , AlSufiani Fahd , Aloraidi Ahmed
Published: October 2024

Background: Schwannomas are well‐encapsulated, solitary tumors that grow slowly from the nerve sheath. Sellar schwannomas tend to be mistaken for other sellar/parasellar lesions due to similar clinical and radiological findings. The present article describes the clinical presentation, radiological findings, histopathological features, and outcome of a patient with sellar schwannoma.

Case Description: A 23‐year‐old female, known to have hypothyroidism secondary to Hashimoto’s thyroiditis, presented with multiple episodes of galactorrhea, weight gain, and irregular menstrual cycle for 8 months. It was associated with decreased visual acuity and episodic headaches. Neurological examination revealed no focal deficits. Brain magnetic resonance imaging (MRI) showed a well‐defined lobulated lesion in the sellar region, compressing the right optic nerve and optic chiasm. The patient underwent craniotomy and tumor resection. The histopathological sections were diagnostic of schwannoma. Postoperatively, the patient noted a subjective improvement in her visual acuity. She was discharged in stable condition with regular follow‐ups at neurosurgery, endocrine, and ophthalmology clinics.

Conclusion: Schwannoma of the sellar region is rare and can be misdiagnosed as pituitary adenomas. Preoperative hormonal profile and meticulous neuroradiological assessment narrow down the differential diagnosis for patients with sellar lesions. The diagnosis of sellar schwannomas is established with histopathology and immunohistochemistry results.
Bacterial Analysis of the Whole Blood in Chinese Healthy Donors Using 16S rDNA–Targeted Metagenomic Sequencing
Authors: Zhang Jingjing , He Yanmin , Chen Chen , Hu Wei , He Ji , Ying Yanling , Zhu Faming
Published: October 2024

Background: The presence of bacteria in the blood of healthy individuals remains controversial. This study explored the comprehensive bacterial profiles and specific biomarkers in different components of healthy Chinese blood donors.

Methods: A total of 5230 whole blood (WB) specimens were collected. Among them, 5200 random samples were pooled into 26 mixed samples for bacterial profile analysis. The remaining 30 random samples were divided into 4 groups based on components: WB, plasma, red blood cells (RBCs), and buffy coat (BC). Subsequently, the amplicons of the bacterial 16S rDNA V3–V4 fragments were sequenced to measure the diversity and composition of the bacteria using next‐generation sequencing.

Results: The bacterial DNAs in the blood primarily originated from the Proteobacteria phylum. A total of 301 species of bacterial DNA were found in blood specimens, with 46 species being present among all groups. A significantly higher abundance of bacterial DNA was found in the plasma and RBCs compared to those in BC and WB. However, the plasma and RBC groups showed significantly higher species diversity and richness compared to the BC and WB groups. In addition, the WB group had a significantly different community structure and composition compared to the plasma and RBC groups but was similar to the BC group.

Conclusion: The presence of bacterial DNA fragments was confirmed in blood from healthy Chinese donors. The bacterial DNA fragments enriched in plasma showed the highest diversity, followed by RBC, WB, and BC. These results provide a foundation for further research on the microbiome in the blood of healthy individuals.
The Stationary Distribution and Extinction of a Stochastic Five‐Dimensional COVID‐19 Model
Authors: Memet Ehbal , Abdurahman Xamxinur , Muhammadhaji Ahmadjan
Published: October 2024

This paper investigates a stochastic SEIAIR epidemic model with nonlinear incidence and contacting distance to describe the transmission dynamics of COVID‐19. Firstly, we show the global existence of positive solution of the system. Then, using the Lyapunov function method and theory of stochastic analysis, we set out the sufficient conditions of the existence and uniqueness of an ergodic stationary distribution to the stochastic model. Furthermore, we obtain the sufficient condition for extinction of the disease. Finally, we go through some numerical simulations to demonstrate the theoretical results. Our study extends and improves the results of previous studies.
Flutter Suppression Effects of Movable Vertical Stabilizers on Suspension Bridges With Steel Box Girders
Authors: Zhou Rui , Xiao Dong , Fang Genshen , Yang Yongxin , Ge Yaojun , Xu Haojun , Wu Yufei
Published: October 2024

As the combination of springs and vertical stabilizers, the movable downward vertical central stabilizer (MDVCS) is proposed to further control the nonlinear flutter of super long‐span suspension bridges in this paper. A series of flutter suppression tests of closed‐box girders and twin‐box steel girders with various MDVCSs are conducted. Based on the coupled flutter theoretical method, the sensitivity analysis of two important parameters including the height and stiffness of MDVCS are carried out to compare their nonlinear flutter control mechanism. The results show that the flutter critical wind speed (Ucr) of the closed‐box girder continued to increase with the decrease of the height of the DVCS and the increase of spring stiffness, whereas the Ucr of the twin‐box girder increased at first and then decreased. The cubic polynomial function and quadratic Holliday function are suitable to modify the correction coefficients of Ucr for the closed‐box girder with various stiffnesses and heights of MDVCS, while the Lorentz peak‐value function and cubic polynomial function are suitable to modify the Ucr of the twin‐box girder. Furthermore, the MDVCS significantly changes the rules of two positive and negative aerodynamic damping ratios for the closed‐box girder and two negative aerodynamic damping ratios for the twin‐box girder. Besides, the peak vertical displacement amplitudes of the box girder are about half of the MDVCS, since both the height and stiffness of MDVCS alter the elliptical radius of vertical phase planes to affect the limit cycle oscillation of soft flutter, especially for the leeward MDVCS for the twin‐box girder.
To Develop Biomarkers for Diabetic Nephropathy Based on Genes Related to Fibrosis and Propionate Metabolism and Their Functional Validation
Authors: Li Sha , Chen Jingshan , Zhou Wenjing , Liu Yonglan , Zhang Di , Yang Qian , Feng Yuerong , Cha Chunli , Li Li , He Guoyong , Li Jun
Published: October 2024

Propionate metabolism is important in the development of diabetes, and fibrosis plays an important role in diabetic nephropathy (DN). However, there are no studies on biomarkers related to fibrosis and propionate metabolism in DN. Hence, the current research is aimed at evaluating biomarkers associated with fibrosis and propionate metabolism and to explore their effect on DN progression. The GSE96804 (DN : control = 41 : 20) and GSE104948 (DN : control = 7 : 18) DN‐related datasets and 924 propionate metabolism‐related genes (PMRGs) and 656 fibrosis‐related genes (FRGs) were acquired from the public database. First, DN differentially expressed genes (DN‐DEGs) between the DN and control samples were sifted out via differential expression analysis. The PMRG scores of the DN samples were calculated based on PMRGs. The samples were divided into the high and low PMRG score groups according to the median scores. The PM‐DEGs between the two groups were screened out. Second, the intersection of DN‐DEGs, PM‐DEGs, and FRGs was taken to yield intersected genes. Random forest (RF) and recursive feature elimination (RFE) analyses of the intersected genes were performed to sift out biomarkers. Then, single gene set enrichment analysis was conducted. Finally, immunoinfiltrative analysis was performed, and the transcription factor (TF)–microRNA (miRNA)–mRNA regulatory network and the drug–gene interaction network were constructed. There were 2633 DN‐DEGs between the DN and control samples and 515 PM‐DEGs between the high and low PMRG score groups. In total, 10 intersected genes were gained after taking the intersection of DN‐DEGs, PM‐DEGs, and FRGs. Seven biomarkers, namely, SLC37A4, ACOX2, GPD1, angiotensin‐converting enzyme 2 (ACE2), SLC9A3, AGT, and PLG, were acquired via RF and RFE analyses, and they were found to be involved in various mechanisms such as glomerulus development, fatty acid metabolism, and peroxisome. The seven biomarkers were positively correlated with neutrophils. Moreover, 8 TFs, 60 miRNAs, and 7 mRNAs formed the TF–miRNA–mRNA regulatory network, including USF1‐hsa‐mir‐1296‐5p‐AGT and HIF1A‐hsa‐mir‐449a‐5p‐ACE2. The drug–gene network contained UROKINASE–PLG, ATENOLOL–AGT, and other interaction relationship pairs. Via bioinformatic analyses, the risk of fibrosis and propionate metabolism‐related biomarkers in DN were explored, thereby providing novel ideas for research related to DN diagnosis and treatment.
Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors
Authors: Kawai-Kawachi Asuka , Lenormand Madison M. , Astier Clémence , Herbel Noé , Cutrona Meritxell B. , Ngo Carine , Garrido Marlène , Eychenne Thomas , Dorvault Nicolas , Bordelet Laetitia , Song Feifei , Bouyakoub Ryme , Loktev Anastasia , Romo-Morales Antonio , Henon Clémence , Colmet-Daage Léo , Vibert Julien , Drac Marjorie , Brough Rachel , Schwob Etienne , Martella Oliviano , Pinna Guillaume , Shipley Janet M. , Mittnacht Sibylle , Zimmermann Astrid , Gulati Aditi , Mir Olivier , Le Cesne Axel , Faron Matthieu , Honoré Charles , Lord Christopher J. , Chabanon Roman M. , Postel-Vinay Sophie
Published: October 2024

Desmoplastic small round cell tumor (DSRCT) is an aggressive sarcoma subtype that is driven by the EWS–WT1 chimeric transcription factor. The prognosis for DSRCT is poor, and major advances in treating DSRCT have not occurred for over two decades. To identify effective therapeutic approaches to target DSRCT, we conducted a high-throughput drug sensitivity screen in a DSRCT cell line assessing chemosensitivity profiles for 79 small-molecule inhibitors. DSRCT cells were sensitive to PARP inhibitors (PARPi) and ataxia–telangiectasia and Rad3–related inhibitors (ATRi), as monotherapies and in combination. These effects were recapitulated using multiple clinical PARPi and ATRi in three biologically distinct, clinically relevant models of DSRCT, including cell lines, a patient-derived xenograft–derived organoid model, and a cell line–derived xenograft mouse model. Mechanistically, exposure to a combination of PARPi and ATRi caused increased DNA damage, G2–M checkpoint activation, micronuclei accumulation, replication stress, and R-loop formation. EWS–WT1 silencing abrogated these phenotypes and was epistatic with exogenous expression of the R-loop resolution enzyme RNase H1 in reversing sensitivity to PARPi and ATRi monotherapies. The combination of PARPi and ATRi also induced EWS–WT1–dependent cell-autonomous activation of the cyclic GMP–AMP synthase–stimulator of IFN genes innate immune pathway and cell-surface expression of PD-L1. Taken together, these findings point toward a role for EWS–WT1 in generating R-loop–dependent replication stress that leads to a targetable vulnerability, providing a rationale for the clinical assessment of PARPi and ATRi in DSRCT.

Significance: EWS–WT1, the unique oncogenic driver of desmoplastic small round cell tumors, confers sensitivity to PARP and ATR inhibitors, supporting the potential of these drugs in treating patients with this aggressive sarcoma subtype.
The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields
Authors: Chen Dongjiang , Le Son B. , Manektalia Harshit , Liu Tianyi , Hutchinson Tarun E. , O’Dell Adam , Salhia Bodour , Tran David D.
Published: October 2024

Tumor treating fields (TTFields) use low-intensity, alternating electric fields to exert antitumor activity and have demonstrated efficacy against multiple cancers, including glioblastoma (GBM). Unfortunately, cancer cells inevitably develop resistance to TTFields, highlighting the need to elucidate the underlying mechanisms to develop approaches to induce durable responses. Using a gene network–based machine learning algorithm, we interrogated TTFields-resistant GBM cells and uncovered a regulatory axis anchored by the prostaglandin E2 receptor 3 (EP3) and the transcription factor zinc finger 488 (ZNF488). Mechanistically, TTFields induced EP3 upregulation and nuclear envelope localization, where it formed a complex with ZNF488 to induce resistance to TTFields by promoting self-renewal of glioma stem-like cells (GSC). Overexpression of EP3 and/or ZNF488 in TTFields-sensitive GSC conferred resistance and enhanced self-renewal, whereas expression of noninteracting mutants of these proteins abrogated the formation of the nuclear complex and prevented resistance. Inhibition of either partner in this protein complex in resistant GSC, including those freshly isolated from TTFields-resistant GBM tumors, resensitized cells to the cytotoxic effects of TTFields, concomitant with reduced self-renewal and in vivo tumorigenicity. Importantly, inhibition of EP3 in TTFields-sensitive GSC preemptively halted the development of resistance. The EP3–ZNF488 axis was significantly upregulated in TTFields-resistant GBM tumors, and coexpression of EP3 and ZNF488 in other cancers correlated with lower survival rates. Collectively, these results indicate that the nuclear EP3–ZNF488 axis is necessary and sufficient to establish TTFields resistance, underscoring the potential to target this axis to prevent or reverse resistance in GBM and possibly other cancers.

Significance: The EP3–ZNF488 master regulatory axis in cancer stem-like cells drives resistance to treatments like tumor treating fields, opening avenues for developing strategies to enhance therapeutic efficacy.
Olfactory Epithelium Infection by SARS-CoV-2: Possible Neuroinflammatory Consequences of COVID-19
Authors: Gutiérrez-García Ana G. , Contreras Carlos M.
Published: October 2024

Background: The loss of smell is a typical diagnostic symptom of coronavirus disease 2019 (COVID-19). This sensorial deprivation may be expressed as quantitative (anosmia or hyposmia) or qualitative (dysosmia) alterations as a consequence of anatomical disturbances of the nasal epithelium structure. The olfactory system sends direct neuronal connections to brain structures that are involved in emotional processing, including deep temporal nuclei. This anatomical and functional feature may be related to the occurrence of emotional disorders among COVID-19 patients. Summary: We identify a possible sequence of events, from typical olfactory dysfunction that is associated with COVID-19 and caused by olfactory epithelium damage to disturbances in the quality of life and emotional state of infected patients that is attributable to possible neuroinflammatory processes. Sensorial deprivation causes deleterious actions on mood, negatively affecting quality of life. Olfactory dysfunction that is associated with COVID-19 occurs concurrently with psychological distress, symptoms of anxiety, and depressive disorders and impinges on self-perceived quality of life. Key Messages: Changes in mood are certainly associated with multiple factors, including the environment and isolation, but the observation that the virus may penetrate the central nervous system through the olfactory bulb and the connection between the olfactory system and prefrontal and orbitofrontal cortices and the amygdala-hippocampus do not allow one to discard neural factors that are involved in the pathophysiology of emotional symptoms in post-COVID-19 patients. Behavioral symptoms of COVID-19 involve local olfactory actions and the participation of central neuronal systems.
Tanshinone IIA Inhibits Hydrogen Peroxide-Induced Ferroptosis in Melanocytes through Activating Nrf2 Signaling Pathway
Authors: Li Xiaosha , Tang Shiyang , Wang Haizhen , Li Xin
Published: October 2024

Introduction: Melanocyte ferroptosis has been proven to contribute to the development of vitiligo. Tanshinone IIA (TSA), a Chinese herbal extract, has been shown to inhibit vitiligo progression. Whether TSA regulates ferroptosis in melanocytes remains unclear. Methods: Hydrogen peroxide (H2O2) was used to induce melanocytes to stimulate vitiligo cell model in vitro. Cell proliferation was examined by 5-ethynyl-2′-deoxyuridine assay. The levels of malondialdehyde, reactive oxygen species, glutathione peroxidase, and iron were detected by corresponding commercial kit. The protein levels of ferroptosis-related markers and Nrf2 pathway-related markers were examined using western blot and immunofluorescence staining. Cell viability and cytotoxicity were analyzed using Cell Counting Kit-8 assay and lactate dehydrogenase detection. Mitochondrial morphology was examined using a transmission electron microscope. Results: After H2O2 treatment, melanocyte proliferation was reduced, while oxidative stress and ferroptosis were enhanced. TSA treatment could inhibit ferroptosis in H2O2-induced melanocytes. Besides, TSA could activate Nrf2 pathway and promote Nrf2 nuclear translocation, and Nrf2-specific inhibitor (ML385) also reversed the inhibitory effect of TSA on H2O2-induced melanocyte ferroptosis. Conclusion: Our data showed that TSA alleviated H2O2-induced melanocyte ferroptosis via activating Nrf2 pathway.
Hypoxia Activates FGF-23-ERK/MAPK Signaling Pathway in Ischemia-Reperfusion-Induced Acute Kidney Injury
Authors: Liu Weihua , Lin Miao , Dai Yiping , Hong Fuyuan
Published: October 2024

Introduction: Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI. Methods: An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF1α, and ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting was used to measure the phosphorylation of extracellular signal-regulated kinase (ERK) level. Results: In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of ERK (p-ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham-operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, GPx, and p-ERK. In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and p-ERK, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells, but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, pro-inflammatory factor levels, oxidative stress response, and p-ERK levels. Conclusion: FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.
Urgent Contrast-Enhanced Computed Tomography before Early Colonoscopy in the Management of Colonic Diverticular Bleeding: A Multicenter Randomized Controlled Trial
Authors: Hirai Yuichiro , Uraoka Toshio , Wada Michiko , Mori Hideki , Fujimoto Ai , Sakakibara Yuko , Toyokawa Tatsuya , Kagaya Takashi , Sasaki Yoshihiro , Mannami Tomohiko , Kuwai Toshio , Watanabe Noriko , Hamada Hiroshige , Esaka Naoki , Kimura Toshihisa , Fujii Hiroyuki , Hosoda Yasuo , Shimada Masaaki , Miyabayashi Hideharu , Somada Shinichi , Mabe Katsuhiro , Inoue Shuji , Saito Hiroki , Furuya Kensuke , Kawamura Norio , Kudo Tomohiro , Hori Keisuke , Sakamoto Naoto , Kato Mototsugu , Higuchi Nobuya , Harada Naohiko ,   the NHO Network Gastrointestinal Study Group
Published: October 2024

Introduction: Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 h of arrival) or other clinical outcomes of CDB. Methods: We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (<30 days) and late (<1 year) rebleeding, length of hospital stay, and transfusion requirements. Results: In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], −7.9 to 12.3; p = 0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, −9.4 to 10.4; p = 1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay, and transfusion requirements. Conclusion: The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN registry number, UMIN000026865).
Identification of Immune-Related Gene Signature Model for Predicting Lung Cancer Survival and Response to Immunotherapy
Authors: Lin Wenrong , Cai XiaoJun , Lin YiJin , Su Weikun , Weng Guibin , Chen Lin , Ding Jianming , Cai Yibin
Published: October 2024

Introduction: Studies have shown that immune-related genes play a crucial role in tumor development and treatment. However, the specific roles and potential value of these genes in lung cancer patients are still not fully understood. Therefore, this study aims to establish a novel risk model based on immune-related genes for evaluating the prognostic risk and response to immune therapy in lung cancer patients. Methods: Gene expression and clinical data of lung cancer patients were retrieved from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, while immune-related genes were obtained from the ImmPort database. A risk signature model was developed using univariate Cox analysis and LASSO regression analysis. The prognostic value of the model and its response to immunotherapy were analyzed by survival analysis, immune infiltration analysis, and immunotherapy response analysis. Results: We have developed a risk signature model based on eight key immune-related genes, which can classify patients into high-risk and low-risk groups. The prognosis of the high-risk group was significantly lower than that of the low-risk group and was validated in multiple GEO datasets. The mutation frequency was lower in the low-risk group compared to the high-risk group (TP53: 55% vs. 65%; TTN: 52% vs. 60%; CSMD3: 34% vs. 45%). Futhermore, CD274 expression was lower in the low-risk patients, and the high-risk patients in the IMvigor210 cohort had lower survival. Immune infiltration analyses showed that the high-risk group was negatively correlated with the infiltration level of B cells, CD4+ T cells, and NK cells. Importantly, patients in the low-risk group exhibit significantly lower TIDE scores, suggesting that they are more responsive to immunotherapy. Conclusion: Our study has established a novel and robust immune-related gene risk model that can assist in evaluating the prognostic risk and immune therapy response of lung cancer patients.