bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-coding RNA alterations in extracellular vesicles from bronchoalveolar lavage fluid contribute to mechanical ventilation-induced pulmonary fibrosis
Authors: Tang Ri , Hu Yue , Mei Shuya , Zhou Yang , Feng Jinhua , Jin Tao , Dai Bo , Xing Shunpeng , Gao Yuan , Xu Qiaoyi , He Zhengyu 
Published: March 2023

ObjectiveFor respiratory failure patients, mechanical ventilation (MV) is a life-saving therapy to maintain respiratory function. However, MV could also cause damage to pulmonary structures, result in ventilator-induced lung injury (VILI) and eventually progress to mechanical ventilation-induced pulmonary fibrosis (MVPF). Mechanically ventilated patients with MVPF are closely related to increased mortality and poor quality of life in long-term survival. Thus, a thorough understanding of the involved mechanism is necessary.MethodsWe used next-generation sequencing to identify differentially expressed non-coding RNAs (ncRNAs) in BALF EVs which were isolated from Sham and MV mice. Bioinformatics analysis was conducted to identify the engaged ncRNAs and related signaling pathways in the process of MVPF.ResultsWe found 1801 messenger RNAs (mRNA), 53 micro RNAs (miRNA), 273 circular RNAs (circRNA) and 552 long non-coding RNAs (lncRNA) in mice BALF EVs of two groups, which showed significant differential expression. TargetScan predicted that 53 differentially expressed miRNAs targeted 3105 mRNAs. MiRanda revealed that 273 differentially expressed circRNAs were associated with 241 mRNAs while 552 differentially expressed lncRNAs were predicated to target 20528 mRNAs. GO, KEGG pathway analysis and KOG classification showed that these differentially expressed ncRNA-targeted mRNAs were enriched in fibrosis related signaling pathways and biological processes. By taking the intersection of miRNAs target genes, circRNAs target genes and lncRNAs target genes, we found 24 common key genes and 6 downregulated genes were confirmed by qRT-PCR.ConclusionsChanges in BALF-EV ncRNAs may contribute to MVPF. Identification of key target genes involved in the pathogenesis of MVPF could lead to interventions that slow or reverse fibrosis progression.
Deletion of NADPH oxidase 2 attenuates cisplatin-induced acute kidney injury through reducing ROS-induced proximal tubular cell injury and inflammation
Authors: Chen Ho-Ching , Hou Hsin-Yu , Sung Junne-Ming , Shieh Chi-Chang 
Published: March 2023

BackgroundsCisplatin is a commonly used chemotherapeutic agent in cancer treatment. However, its high nephrotoxicity limits its therapeutic application and efficacy. Cisplatin induces nephrotoxicity mainly through oxidative stress and inflammation. Reactive oxygen species (ROS) in the kidneys mainly arise from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 2 (NOX2), which is highly upregulated during ischemia-reperfusion injury and diabetes mellitus. However, its role in cisplatin-induced acute kidney injury (AKI) remains unknown.MethodsA 8-10-week-old NOX2 gene-knockout and wild-type mice were injected with 25 mg/kg cisplatin intraperitoneally for experiments.ResultsWe investigated the role of NOX2 in cisplatin-induced AKI and found that NOX2-mediated ROS production is a key inflammatory mediator of proximal tubular cell injury in cisplatin-induced AKI. NOX2 gene-knockout alleviated cisplatin-induced renal function decline, tubular injury score, kidney injury molecule-1(Kim-1) expression, and interleukin (IL)-6 and IL-1α levels with a reduction of ROS production. Moreover, in cisplatin-induced AKI, intercellular adhesion molecule 1 (ICAM-1) and the chemoattractant CXC ligand 1 (CXCL1) were highly expressed in association with neutrophil infiltration, which were all attenuated by deletion of NOX2.ConclusionThese data indicate that NOX2 aggravates cisplatin nephrotoxicity by promoting ROS-mediated tissue injury and neutrophil infiltration. Thus, appropriate targeting of NOX2/ROS pathway may minimize the risk of cisplatin-induced kidney injury in patients receiving cancer therapy.
Changes in retinal circulation and choroidal thickness in patients with acute myeloid leukemia detected by optical coherence tomography angiography
Authors: Yang Ling , Chen Yanwei , Zhang Yunxiang , Shen Ting , Shen Xi 
Published: March 2023

PurposeTo investigate changes in retinal circulation and the choroid in patients with acute myeloid leukemia (AML) in the acute and remission stages, to analyze the correlation between retinal circulation and laboratory parameters, and to assess risk factors associated with leukemic retinopathy.MethodsForty-eight patients (93 eyes) with AML were enrolled and divided into two groups according to fundus examination findings: the retinopathy and no retinopathy groups. Patients underwent eye measurements before treatment and after remission. Macular vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ), and choroidal thickness (ChT) were measured using optical coherence tomography angiography. Patients with healthy eyes were recruited as control participants.ResultsPatients with leukemic retinopathy had higher measurements of white blood cells (WBCs), circulating blasts, fibrin degradation products, and cross-linked fibrin degradation products (D-dimer) and a lower hemoglobin (HB) count (p &lt; 0.05). In the acute phase of the disease, the VD and PD were lower and the ChT was thicker in patients with AML than in controls (p &lt; 0.05), irrespective of the presence of leukemic retinopathy; however, the patients were partially recovered in the remission stage. The VD was lower in patients with higher WBC (r = −0.217, p = 0.036), D-dimer (r = −0.279, p = 0.001), fasting blood glucose (FBG) (r = −0.298, p = 0.004) and triglyceride (r = −0.336, p = 0.001) levels. The FAZ area was negatively correlated with HB (r = −0.258, p = 0.012).ConclusionPatients with AML appear to have subclinical retinal perfusion loss and choroidal thickening in the acute phase of the disease, but this is reversible. Injury to bone marrow function may cause a decrease in retinal perfusion. Leukemic retinopathy is associated with abnormal hematologic parameters and coagulopathy.
Artificial intelligence-based 68Ga-DOTATOC PET denoising for optimizing 68Ge/68Ga generator use throughout its lifetime
Authors: Quak Elske , Weyts Kathleen , Jaudet Cyril , Prigent Anaïs , Foucras Gauthier , Lasnon Charline 
Published: March 2023

IntroductionThe yield per elution of a 68Ge/68Ga generator decreases during its lifespan. This affects the number of patients injected per elution or the injected dose per patient, thereby negatively affecting the cost of examinations and the quality of PET images due to increased image noise. We aimed to investigate whether AI-based PET denoising can offset this decrease in image quality parameters.MethodsAll patients addressed to our PET unit for a 68Ga-DOTATOC PET/CT from April 2020 to February 2021 were enrolled. Forty-four patients underwent their PET scans according to Protocol_FixedDose (150 MBq) and 32 according to Protocol_WeightDose (1.5 MBq/kg). Protocol_WeightDose examinations were processed using the Subtle PET software (Protocol_WeightDoseAI). Liver and vascular SUV mean were recorded as well as SUVmax, SUVmean and metabolic tumour volume (MTV) of the most intense tumoural lesion and its background SUVmean. Liver and vascular coefficients of variation (CV), tumour-to-background and tumour-to-liver ratios were calculated.ResultsThe mean injected dose of 2.1 (0.4) MBq/kg per patient was significantly higher in the Protocol_FixedDose group as compared to 1.5 (0.1) MBq/kg for the Protocol_WeightDose group. Protocol_WeightDose led to noisier images than Protocol_FixedDose with higher CVs for liver (15.57% ± 4.32 vs. 13.04% ± 3.51, p = 0.018) and blood-pool (28.67% ± 8.65 vs. 22.25% ± 10.37, p = 0.0003). Protocol_WeightDoseAI led to less noisy images than Protocol_WeightDose with lower liver CVs (11.42% ± 3.05 vs. 15.57% ± 4.32, p &lt; 0.0001) and vascular CVs (16.62% ± 6.40 vs. 28.67% ± 8.65, p &lt; 0.0001). Tumour-to-background and tumour-to-liver ratios were lower for protocol_WeightDoseAI: 6.78 ± 3.49 vs. 7.57 ± 4.73 (p = 0.01) and 5.96 ± 5.43 vs. 6.77 ± 6.19 (p &lt; 0.0001), respectively. MTVs were higher after denoising whereas tumour SUVmax were lower: the mean% differences in MTV and SUVmax were + 11.14% (95% CI = 4.84–17.43) and −3.92% (95% CI = −6.25 to −1.59).ConclusionThe degradation of PET image quality due to a reduction in injected dose at the end of the 68Ge/68Ga generator lifespan can be effectively counterbalanced by using AI-based PET denoising.
Early diagnosis of neural impairment in seropositive leprosy household contacts: The experience of a reference center in Brazil
Authors: dos Santos Diogo Fernandes , Garcia Leonardo Peixoto , Borges Isabella Sabião , Oliveira Thales Junqueira , Antunes Douglas Eulálio , Luppi Andrea De Martino , Goulart Isabela Maria Bernardes 
Published: March 2023

IntroductionLeprosy is an infectious disease that remains with a high number of new cases in developing countries. Household contacts have a higher risk for the development of the disease, but the neural impairment in this group is not well elucidated yet. Here, we measured the chance of occurrence of peripheral neural impairment in asymptomatic leprosy household.MethodsContacts who present anti-PGL-I IgM seropositivity, through electroneuromyography (ENMG) evaluation. We recruited 361 seropositive contacts (SPC) from 2017 to 2021, who were subjected to an extensive protocol that included clinical, molecular, and electroneuromyographic evaluations.ResultsOur data revealed a positivity of slit skin smear and skin biopsy qPCR of 35.5% (128/361) and 25.8% (93/361) respectively. The electroneuromyographic evaluation of the SPC showed neural impairment in 23.5% (85/361), with the predominance of a mononeuropathy pattern in 62.3% (53/85). Clinical neural thickening was observed in 17.5% (63/361) of seropositive contacts, but among the individuals with abnormal ENMG, only 25.9% (22/85) presented neural thickening in the clinical exam.DiscussionOurs results corroborates the need to make the approach to asymptomatic contacts in endemic countries more timely. Since leprosy in its early stages can present an indolent and subclinical evolution, serological, molecular, and neurophysiological tools are essential to break the disease transmission chain.
Association of smoking with the survival of patients with brain metastasis of lung cancer
Authors: Yu Jiayi , Zhang Yu , Liu Zheran , He Yan , Pei Yiyan , Zhang Renjie , Peng Xingchen , Fang Fang 
Published: March 2023

BackgroundSmoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients.MethodsThis study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint.ResultsOf the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p &lt; 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p&lt;0.01] had an increased risk of death. However, quitting smoking was not associated with improved survival [HR, 0.90 (95% CI, 0.77-1.04), p = 0.16]. The overall survival increased with the increase of smoking cessation years.ConclusionsIn lung cancer patients with brain metastases, smoking was associated with an increased risk of death, but quitting smoking was not associated with improved survival.
Comparison between audio-vestibular findings and contrast-enhanced MRI of inner ear in patients with unilateral Ménière’s disease
Authors: Leng Yangming , Fan Wenliang , Liu Yingzhao , Xia Kaijun , Zhou Renhong , Liu Jingjing , Wang Hongchang , Ma Hui , Liu Bo 
Published: March 2023

ObjectiveThe diagnosis of Ménière’s disease (MD), characterized by idiopathic endolymphatic hydrops (ELH), remains a clinical priority. Many ancillary methods, including the auditory and vestibular assessments, have been developed to identify ELH. The newly emerging delayed magnetic resonance imaging (MRI) of the inner ear after intratympanic gadolinium (Gd) has been used for identifying ELH in vivo. We aimed to investigate the concordance of audio-vestibular and radiological findings in patients with unilateral MD.MethodsIn this retrospective study, 70 patients with unilateral definite MD underwent three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences following intratympanic application of Gd. Audio-vestibular evaluations were performed, including pure tone audiometry, electrocochleogram (ECochG), glycerol test, caloric test, cervical and ocular vestibular evoked myogenic potentials (VEMPs), and video head impulse test (vHIT). The relationship between imaging signs of ELH and audio-vestibular results was investigated.ResultsThe incidence of radiological ELH was higher than that of neurotological results, including the glycerol test, caloric test, VEMPs, and vHIT. Poor or slight agreement was observed between audio-vestibular findings and radiological ELH in cochlear and/or vestibular (kappa values &lt;0.4). However, the pure tone average (PTA) in the affected side significantly correlated with the extent of both cochlear (r = 0.26795, p = 0.0249) and vestibular (r = 0.2728, p = 0.0223) hydrops. Furthermore, the degree of vestibular hydrops was also positively correlated with course duration (r = 0.2592, p = 0.0303) and glycerol test results (r = 0.3944, p = 0.0061) in the affected side.ConclusionIn the diagnosis of MD, contrast-enhanced MRI of the inner ear is advantageous in detecting ELH over the conventional audio-vestibular evaluations, which estimates more than hydropic dilation of endolymphatic space.
An absolute approach to using whole exome DNA and RNA workflow for cancer biomarker testing
Authors: Malhotra Richa , Javle Vyomesh , Tanwar Nishtha , Gowda Pooja , Varghese Linu , K Anju , Madhusudhan Nandhitha , Jaiswal Nupur , K. S. Bhargavi , Chatterjee Manjima , Prabhash Kumar , Sreekanthreddy Peddagangannagari , Rishi Kshitij D. , Goswami Hitesh M. , Veldore Vidya H. 
Published: March 2023

IntroductionThe concept of personalized medicine in cancer has emerged rapidly with the advancement of genome sequencing and the identification of clinically relevant variants that contribute to disease prognosis and facilitates targeted therapy options. In this study, we propose to validate a whole exome-based tumor molecular profiling for DNA and RNA from formalin-fixed paraffin-embedded (FFPE) tumor tissue.MethodsThe study included 166 patients across 17 different cancer types. The scope of this study includes the identification of single-nucleotide variants (SNVs), insertions/deletions (INDELS), copy number alterations (CNAs), gene fusions, tumor mutational burden (TMB), and microsatellite instability (MSI). The assay yielded a mean read depth of 200×, with &gt;80% of on-target reads and a mean uniformity of &gt;90%. Clinical maturation of whole exome sequencing (WES) (DNA and RNA)- based assay was achieved by analytical and clinical validations for all the types of genomic alterations in multiple cancers. We here demonstrate a limit of detection (LOD) of 5% for SNVs and 10% for INDELS with 97.5% specificity, 100% sensitivity, and 100% reproducibility.ResultsThe results were &gt;98% concordant with other orthogonal techniques and appeared to be more robust and comprehensive in detecting all the clinically relevant alterations. Our study demonstrates the clinical utility of the exome-based approach of comprehensive genomic profiling (CGP) for cancer patients at diagnosis and disease progression.DiscussionThe assay provides a consolidated picture of tumor heterogeneity and prognostic and predictive biomarkers, thus helping in precision oncology practice. The primary intended use of WES (DNA+RNA) assay would be for patients with rare cancers as well as for patients with unknown primary tumors, and this category constitutes nearly 20–30% of all cancers. The WES approach may also help us understand the clonal evolution during disease progression to precisely plan the treatment in advanced stage disease.
Heterogeneity of tumour mutational burden in metastatic NSCLC demonstrated by endobronchial ultrasound sampling
Authors: Leong Tracy L. , Aloe Christian , Aujla Savreet , Wang Hao , Gayevskiy Velimir , Asselin-Labat Marie-Liesse , Gray Lesley-Ann , Steinfort Daniel , Bozinovski Steven 
Published: March 2023

IntroductionTumour mutational burden (TMB) is an important emerging biomarker for immune checkpoint inhibitors (ICI). The stability of TMB values across distinct EBUS tumour regions is not well defined in advanced lung cancer patients.MethodsThis study included a whole-genome sequencing cohort (n=11, LxG cohort) and a targeted Oncomine TML panel cohort (n=10, SxD cohort), where paired primary and metastatic samples were obtained by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA).ResultsThe LxG cohort displayed a strong correlation between the paired primary and metastatic sites, with a median TMB score of 7.70 ± 5.39 and 8.31 ± 5.88 respectively. Evaluation of the SxD cohort demonstrated greater inter-tumoural TMB heterogeneity, where Spearman correlation between the primary and metastatic sites fell short of significance. Whilst median TMB scores were not significantly different between the two sites, 3 out of 10 paired samples were discordant when using a TMB cut-off of 10 mutations per Mb. In addition, PD-L1 copy number and KRAS mutations were assessed, demonstrating the feasibility of performing multiple molecular tests relevant to ICI treatment using a single EBUS sample. We also observed good consistency in PD-L1 copy number and KRAS mutation, where cut-off estimates were consistent across the primary and metastatic sites.ConclusionsAssessment of TMB acquired by EBUS from multiple sites is highly feasible and has the potential to improve accuracy of TMB panels as a companion diagnostic test. We demonstrate similar TMB values across primary and metastatic sites, however 3 out of 10 samples displayed inter-tumoural heterogeneity that would alter clinical management.
The mechanism of action of paeoniae radix rubra–angelicae sinensis radix drug pair in the treatment of rheumatoid arthritis through PI3K/AKT/NF-κB signaling pathway
Authors: Li Jia , Zhang Xiaofei , Guo Dongyan , Shi Yajun , Zhang Shihao , Yang Ruiying , Cheng Jiangxue 
Published: March 2023

Objective: To investigate the effects and mechanisms of Paeoniae radix rubra–Angelicae sinensis radix (P-A) drug pair in the treatment of rheumatoid arthritis (RA).Methods: Mass spectrometry was employed to accurately characterize the main components of the P-A drug pair. Network pharmacology was used to analyze the main components and pathways of the P-A drug pair in the treatment of RA, and Discovery Studio software was used to molecularly dock the key proteins on the pathway with their corresponding compounds. The levels of serum TNF-a, IL-1β, and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). The histopathology of the ankle joint was observed by hematoxylin-eosin (HE) staining, and the positive expression of p-PI3K, p-IKK, p-NF-κB, and p-AKT in the synovial tissue of the ankle joint was detected by immunohistochemical analysis. Finally, the expression of PI3K, IKK, and AKT and their phosphorylation levels were determined by western blot in each group of rats.Results: Network pharmacology combined with molecular docking analysis revealed that the pharmacodynamic mechanism of the P-A drug pair for the treatment of RA may be related to the contents of caffeic acid, quercetin, paeoniflorin, and baicalein in the regulation of the expression of the PI3K/AKT/NF-κB signaling pathway and the targets of PIK3CA, PIK3R1, AKT1, HSP90AA1 and IKBKB in the pathway. Compared with the model group, the P-A drug pair significantly improved the pathological changes of the synovial tissue and reduced feet swelling in RA model rats. Moreover, it regulated the levels of TNF-α, IL-1β, and IL-6 in serum (p &lt; 0.05). The results of the immunohistochemical analysis and western blot showed that the expression of PI3K, IKK, NF-κB, and AKT decreased after phosphorylation in the synovial tissue (p &lt; 0.05).Conclusion: The P-A drug pair exhibited an inhibitory effect on the hyperactivation of the PI3K/AKT/NF-κB signaling pathway in the synovial membrane of RA rats. The mechanism may be related to the downregulation of the phosphorylation levels PI3K, IKK, NF-κB, and AKT, which in turn decreased inflammatory cell infiltration and synovial membrane proliferation.
ALDH2 attenuates myocardial pyroptosis through breaking down Mitochondrion-NLRP3 inflammasome pathway in septic shock
Authors: Zhang Ying , Lv Ying , Zhang Qingju , Wang Xingfang , Han Qi , Liang Yan , He Simeng , Yuan Qiuhuan , Zheng Jiaqi , Xu Changchang , Zhang Xiangxin , Wang Zichen , Yu Huaxiang , Xue Li , Wang Jiali , Xu Feng , Pang Jiaojiao , Chen Yuguo 
Published: March 2023

Cell survival or death is critical for cardiac function. Myocardial pyroptosis, as a newly recognized programmed cell death, remains poorly understood in sepsis. In this study, we evaluated the effect of aldehyde dehydrogenase (ALDH2) on myocardial pyroptosis and revealed the underlying mechanisms in sepsis. We established a septic shock mice model by intraperitoneal injection of Lipopolysaccharide (LPS, 15 mg/kg) 12 h before sacrifice. It was found that aldehyde dehydrogenase significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation and Caspase-1/GSDMD-dependent pyroptosis, which remarkably improved survival rate and septic shock-induced cardiac dysfunction, relative to the control group. While aldehyde dehydrogenase knockout or knockdown significantly aggravated these phenomena. Intriguingly, we found that aldehyde dehydrogenase inhibited LPS-induced deacetylation of Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex α subunit (HADHA) by suppressing the translocation of Histone deacetylase 3 (HDAC3) from nuclei to mitochondria. Acetylated HADHA is essential for mitochondrial fatty acid β-oxidation, and its interruption can result in accumulation of toxic lipids, induce mROS and cause mtDNA and ox-mtDNA release. Our results confirmed the role of Histone deacetylase 3 and HADHA in NOD-like receptor protein 3 inflammasome activation. Hdac3 knockdown remarkedly suppressed NOD-like receptor protein 3 inflammasome and pyroptosis, but Hadha knockdown eliminated the effect. aldehyde dehydrogenase inhibited the translocation of Histone deacetylase 3, protected ac-HADHA from deacetylation, and significantly reduced the accumulation of toxic aldehyde, and inhibited mROS and ox-mtDNA, thereby avoided NOD-like receptor protein 3 inflammasome activation and pyroptosis. This study provided a novel mechanism of myocardial pyroptosis through mitochondrial Histone deacetylase 3/HADHA- NOD-like receptor protein 3 inflammasome pathway and demonstrated a significant role of aldehyde dehydrogenase as a therapeutic target for myocardial pyroptosis in sepsis.