bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of epidemiological trends of and associated factors for tooth loss among 35- to 44-year-old adults in Guangdong, Southern China, 1995–2015: a population-based cross-sectional survey
Authors: Jiang Linxin , Li Jianbo , Yang Zijing , Huang Xiaoyan , Zhong Xiong , Huang Yi , Liu Bincheng , Wu Linmei , Huang Shaohong , Fan Weihua 
Published: February 2023

Abstract
Background
Tooth loss is a known marker of oral and systemic health, but large-scale population-based and cross-sectional multi-year comparative studies on tooth loss have yet to be much studied in China. This study explores the changing trends in tooth loss status and the associated factors influencing the prevalence of tooth loss over the past two decades in Guangdong, Southern China.

Methods
Data from three cross-sectional, representative oral epidemiological surveys in Guangdong Province were analyzed, including 400 in 1995, 720 in 2005, and 288 in 2015, for a total of 1408 participants. Sample selection is based on the National Census of China published by the National Bureau of Statistics. In this study, each year, the number of missing teeth (MT) and the prevalence of tooth loss (MT > 0) were calculated. Basic demographic information, socioeconomic status, caries and periodontal status, personal lifestyle factors, and dental health care behaviors were analyzed by multivariate logistic regression to estimate their associations with tooth loss. Statistical significance was evaluated with 2-sided tests with a significance level of P < 0.05.

Results
This study found that the mean number of missing teeth and the prevalence of tooth loss among adults aged 35–44 years in Guangdong Province did not change significantly in the first decade (1995–2005) but decreased significantly in the second decade (2005–2015) (0.94 and 40.8% in 1995, 0.99 and 42.9% in 2005, and 0.63 and 33.3% in 2015, respectively). The mean number of MT by tooth position was highest for the first and second molars, and both were larger in the mandible than in the maxilla. In 1995, populations with low educational attainment and the presence of caries or periodontal pocket (periodontal probing depth ≥ 4 mm) were associated with a higher chance of MT > 0. In 2005, those with low educational attainment, the presence of caries, and 40–44 years old were associated with a higher chance of MT > 0. Moreover, in 2015, females, rural residents, and those with caries or periodontal pocket were associated with a higher chance of MT > 0.

Conclusions
Although tooth retention has improved recently (2005–2015) and the preventive effect of education level on tooth loss has increased over time, efforts to prevent tooth loss in adults need to be strengthened. Particular attention should be given to preventive interventions for women, rural residents, and those suffering from caries or periodontal pocket.
Intraluminal chloride regulates lung branching morphogenesis: involvement of PIEZO1/PIEZO2
Authors: Gonçalves Ana N. , Moura Rute S. , Correia-Pinto Jorge , Nogueira-Silva Cristina 
Published: February 2023

Abstract
Background
Clinical and experimental evidence shows lung fluid volume as a modulator of fetal lung growth with important value in treating fetal lung hypoplasia. Thus, understanding the mechanisms underlying these morphological dynamics has been the topic of multiple investigations with, however, limited results, partially due to the difficulty of capturing or recapitulating these movements in the lab. In this sense, this study aims to establish an ex vivo model allowing the study of lung fluid function in branching morphogenesis and identify the subsequent molecular/ cellular mechanisms.

Methods
Ex vivo lung explant culture was selected as a model to study branching morphogenesis, and intraluminal injections were performed to change the composition of lung fluid. Distinct chloride (Cl−) concentrations (5.8, 29, 143, and 715 mM) or Cl− channels inhibitors [antracene-9-carboxylic acid (A9C), cystic fibrosis transmembrane conductance regulator inhibitor172 (CFTRinh), and calcium-dependent Cl− channel inhibitorA01 (CaCCinh)] were injected into lung lumen at two timepoints, day0 (D0) and D2. At D4, morphological and molecular analyses were performed in terms of branching morphogenesis, spatial distribution (immunofluorescence), and protein quantification (western blot) of mechanoreceptors (PIEZO1 and PIEZO2), neuroendocrine (bombesin, ghrelin, and PGP9.5) and smooth muscle [alpha-smooth muscle actin (α-SMA) and myosin light chain 2 (MLC2)] markers.

Results
For the first time, we described effective intraluminal injections at D0 and D2 and demonstrated intraluminal movements at D4 in ex vivo lung explant cultures. Through immunofluorescence assay in in vivo and ex vivo branching morphogenesis, we show that PGP9.5 colocalizes with PIEZO1 and PIEZO2 receptors. Fetal lung growth is increased at higher [Cl−], 715 mM Cl−, through the overexpression of PIEZO1, PIEZO2, ghrelin, bombesin, MLC2, and α-SMA. In contrast, intraluminal injection of CFTRinh or CaCCinh decreases fetal lung growth and the expression of PIEZO1, PIEZO2, ghrelin, bombesin, MLC2, and α-SMA. Finally, the inhibition of PIEZO1/PIEZO2 by GsMTx4 decreases branching morphogenesis and ghrelin, bombesin, MLC2, and α-SMA expression in an intraluminal injection-independent manner.

Conclusions
Our results identify PIEZO1/PIEZO2 expressed in neuroendocrine cells as a regulator of fetal lung growth induced by lung fluid.
Molecular mechanisms of microRNA-216a during tumor progression
Authors: Hamidi Amir Abbas , Taghehchian Negin , Zangouei Amir Sadra , Akhlaghipour Iman , Maharati Amirhosein , Basirat Zahra , Moghbeli Meysam 
Published: February 2023

AbstractMicroRNAs (miRNAs) as the members of non-coding RNAs family are involved in post-transcriptional regulation by translational inhibiting or mRNA degradation. They have a critical role in regulation of cell proliferation and migration. MiRNAs aberrations have been reported in various cancers. Considering the importance of these factors in regulation of cellular processes and their high stability in body fluids, these factors can be suggested as suitable non-invasive markers for the cancer diagnosis. MiR-216a deregulation has been frequently reported in different cancers. Therefore, in the present review we discussed the molecular mechanisms of the miR-216a during tumor progression. It has been reported that miR-216a mainly functioned as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review paves the way to suggest the miR-216a as a probable therapeutic and diagnostic target in cancer patients.
Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer
Authors: Huang Haoying , Yi Xiaohan , Wei Qingyun , Li Mengyuan , Cai Xueting , Lv Yan , Weng Ling , Mao Yujie , Fan Weiwei , Zhao Mengmeng , Weng Zhongpei , Zhao Qing , Zhao Kewei , Cao Meng , Chen Jing , Cao Peng 
Published: February 2023

AbstractClinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3). siSTAT3 loaded KEVs (STAT3/KEVs) could be easily endowed with EGFR targeting ability (STAT3/EKEVs) and fluorescence by surface modification with tailor-making aptamer through hydrophobic interaction. STAT3/EKEVs with a controlled size of 186 nm displayed excellent stability, high specificity and good cytotoxicity towards EGFR over-expressing and mutant PC9-GR4-AZD1 cells. Intriguingly, the systemic administration of STAT3/EKEVs significantly suppressed subcutaneous PC9-GR4-AZD1 tumor xenografts in nude mice by STAT3 mediated apoptosis. This safe and robust KEVs has emerged as the next generation of gene delivery platform for NSCLC therapy after multiple drug-resistance.
Graphical Abstract
Circular RNA 0001789 sponges miR-140-3p and regulates PAK2 to promote the progression of gastric cancer
Authors: You Jun , Chen Yinan , Chen Donghan , Li Yongwen , Wang Tinghao , Zhu Jingtao , Hong Qingqi , Li Qiyuan 
Published: February 2023

Abstract
Background
Gastric cancer (GC) is the third-leading cause of cancer-associated mortalities globally. The deregulation of circular RNAs (circRNAs) and microRNAs (miRNAs or miRs) is widely implicated in the pathogenesis and progression of different cancer types.

Methods
The expression profiling of circRNAs in GC is required to identify crucial circRNAs as biomarkers or therapeutic targets. In the present study, a published circRNA microarray dataset was used to identify differentially expressed circRNAs between GC tissues and normal gastric mucosa tissues. Reverse transcription-quantitative PCR was performed to validate the expression of circ_0001789. Fisher’s exact test, receiver operating characteristic curve and Kaplan-Meier plots were employed to analyze the clinical significance of circ_0001789. The miRNA targets of circ_0001789 were predicted using an online database, and their functional interaction was further confirmed by RNA pull-down, RNA immunoprecipitation and dual luciferase reporter assays. Transwell assays were conducted to investigate the biological functions of circ_0001789, miR-140-3p and p21 activated kinase 2 (PAK2) in the migration and invasion of GC cells. A xenograft mouse model was established to validate the role of circ_0001789 in the tumorigenesis of GC cells.

Results
circ_0001789 was identified as a highly expressed circRNA in GC tissues versus normal gastric mucosa tissues. Silencing circ_0001789 attenuated the malignancy of GC cells, and exosomal circ_0001789 was sufficient to regulate the malignant phenotype of GC cells. miR-140-3p was further identified as a downstream target of circ_0001789, which showed a negative correlation with circ_0001789 expression in GC tissues. Overexpression of miR-140-3p suppressed cell migration, invasion and epithelial-mesenchymal transition in GC cells. PAK2 was identified as the target of miR-140-3 to mediate the malignant phenotype of GC cells.

Conclusion
The present data suggested that the upregulation of circ_0001789 was associated with the progression of GC and with poor prognosis in patients with GC, and that miR-140-3p/PAK2 served as the downstream axis to mediate the oncogenic effect of circ_0001789.
FYN: emerging biological roles and potential therapeutic targets in cancer
Authors: Peng SanFei , Fu Yang 
Published: February 2023

AbstractSrc family protein kinases (SFKs) play a key role in cell adhesion, invasion, proliferation, survival, apoptosis, and angiogenesis during tumor development. In humans, SFKs consists of eight family members with similar structure and function. There is a high level of overexpression or hyperactivity of SFKs in tumor, and they play an important role in multiple signaling pathways involved in tumorigenesis. FYN is a member of the SFKs that regulate normal cellular processes. Additionally, FYN is highly expressed in many cancers and promotes cancer growth and metastasis through diverse biological functions such as cell growth, apoptosis, and motility migration, as well as the development of drug resistance in many tumors. Moreover, FYN is involved in the regulation of multiple cancer-related signaling pathways, including interactions with ERK, COX-2, STAT5, MET and AKT. FYN is therefore an attractive therapeutic target for various tumor types, and suppressing FYN can improve the prognosis and prolong the life of patients. The purpose of this review is to provide an overview of FYN’s structure, expression, upstream regulators, downstream substrate molecules, and biological functions in tumors.
ASC specks exacerbate α‑synuclein pathology via amplifying NLRP3 inflammasome activities
Authors: Zheng Ran , Yan Yiqun , Dai Shaobing , Ruan Yang , Chen Ying , Hu Chenjun , Lin Zhihao , Xue Naijia , Song Zhe , Liu Yi , Zhang Baorong , Pu Jiali 
Published: February 2023

Abstract
Background
Inflammasome activation has a pathogenic role in Parkinson’s disease (PD). Up-regulated expressions of inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and assembly of ASC specks have been observed in postmortems of human PD brains and experimental PD models. Extracellular ASC specks behave like danger signals and sustain prolonged inflammasome activation. However, the contribution of ASC specks in propagation of inflammasome activation and pathological progression in PD has not been fully established.

Methods
Herein, we used human A53T mutant α-synuclein preformed fibrils (PFFs)-stimulated microglia in vitro and unilateral striatal stereotaxic injection of PFFs-induced mice model of PD in vivo, to investigate the significance of ASC specks in PD pathological progression. Rotarod and open-field tests were performed to measure motor behaviors of indicated mice. Changes in the molecular expression were evaluated by immunofluorescence and immunoblotting (IB). Intracellular knockdown of the ASC in BV2 cells was performed using si-RNA. Microglial and neuronal cells were co-cultured in a trans-well system to determine the effects of ASC knockdown on cytoprotection.

Results
We observed a direct relationship between levels of ASC protein and misfolded α‑synuclein aggregates in PD mice brains. ASC specks amplified NLRP3 inflammasome activation driven by α-synuclein PFFs stimulation, which aggravated reactive microgliosis and accelerated α‑synuclein pathology, dopaminergic neurodegeneration and motor deficits. Endogenous ASC knockdown suppressed microglial inflammasome activation and neuronal α‑synuclein aggregation.

Conclusions
In conclusion, our study elucidated that ASC specks contribute to the propagation of inflammasome activation-associated α‑synuclein pathology in PD, which forms the basis for targeting ASC as a potential therapy for PD.
3D-GBS: a universal genotyping-by-sequencing approach for genomic selection and other high-throughput low-cost applications in species with small to medium-sized genomes
Authors: de Ronne Maxime , Légaré Gaétan , Belzile François , Boyle Brian , Torkamaneh Davoud 
Published: February 2023

AbstractDespite the increased efficiency of sequencing technologies and the development of reduced-representation sequencing (RRS) approaches allowing high-throughput sequencing (HTS) of multiplexed samples, the per-sample genotyping cost remains the most limiting factor in the context of large-scale studies. For example, in the context of genomic selection (GS), breeders need genome-wide markers to predict the breeding value of large cohorts of progenies, requiring the genotyping of thousands candidates. Here, we introduce 3D-GBS, an optimized GBS procedure, to provide an ultra-high-throughput and ultra-low-cost genotyping solution for species with small to medium-sized genome and illustrate its use in soybean. Using a combination of three restriction enzymes (PstI/NsiI/MspI), the portion of the genome that is captured was reduced fourfold (compared to a “standard” ApeKI-based protocol) while reducing the number of markers by only 40%. By better focusing the sequencing effort on limited set of restriction fragments, fourfold more samples can be genotyped at the same minimal depth of coverage. This GBS protocol also resulted in a lower proportion of missing data and provided a more uniform distribution of SNPs across the genome. Moreover, we investigated the optimal number of reads per sample needed to obtain an adequate number of markers for GS and QTL mapping (500–1000 markers per biparental cross). This optimization allows sequencing costs to be decreased by ~ 92% and ~ 86% for GS and QTL mapping studies, respectively, compared to previously published work. Overall, 3D-GBS represents a unique and affordable solution for applications requiring extremely high-throughput genotyping where cost remains the most limiting factor.
PrehospitaL Ultrasound in Undifferentiated DyspnEa (PreLUDE): a prospective, clinical, observational study
Authors: Gundersen Elise Arem , Juhl-Olsen Peter , Bach Allan , Rostgaard-Knudsen Martin , Nielsen Bent Roni Ranghøj , Skaarup Søren Helbo , Petersen Henrik Ømark , Fjølner Jesper , Poulsen Morten Gustav Gerstrøm , Bøtker Morten Thingemann 
Published: February 2023

Abstract
Background
Diagnostic uncertainty in patients with dyspnea is associated with worse outcomes. We hypothesized that prehospital point-of-care ultrasound (POCUS) can improve diagnostic accuracy.

Methods
Prospective observational study of adult patients suffering dyspnea. Prehospital critical care physicians registered a suspected diagnosis based on clinical examination alone, performed POCUS of the heart and lungs, and finally registered suspected diagnoses based on their clinical examination supplemented with POCUS. Pre- and post-POCUS diagnoses were compared to endpoint committee adjudicated diagnoses. The primary outcome was improved sensitivity for diagnosing acute heart failure. Secondary outcomes included other diagnostic accuracy measures in relation to acute heart failure and other causes of dyspnea.

Results
In total, 214 patients were included. The diagnosis of acute heart failure was suspected in 64/214 (30%) of patients before POCUS and 64/214 (30%) patients after POCUS, but POCUS led to reclassification in 53/214 (25%) patients. The endpoint committee adjudicated the diagnosis of acute heart failure in 87/214 (41%) patients. The sensitivity for the diagnosis of acute heart failure was 58% (95% CI 46%–69%) before POCUS compared to 65% (95% CI 53%–75%) after POCUS (p = 0.12). ROC AUC for the diagnosis acute heart failure was 0.72 (95% CI 0.66–0.78) before POCUS compared to 0.79 (0.73–0.84) after POCUS (p < 0.001). ROC AUC for the diagnosis acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) or asthma was 0.87 (0.82–0.91) before POCUS and 0.93 (0.88–0.97) after POCUS (p < 0.001). A POCUS finding of any of severely reduced left ventricular function, bilateral B-lines or bilateral pleural effusion demonstrated the highest sensitivity for acute heart failure at 88% (95% CI 79%–94%), whereas the combination of all of these three findings yielded the highest specificity at 99% (95% CI 95%–100%).

Conclusion
Supplementary prehospital POCUS leads to an improvement of diagnostic accuracy of both heart failure and AE-COPD/-asthma overall described by ROC AUC, but the increase in sensitivity for the diagnoses of acute heart failure did not reach statistical significance. Tailored use of POCUS findings optimizes diagnostic accuracy for rule-out and rule-in of acute heart failure.
Trial registration: Registered in Clinical Trials, 05.04.2019 (identifier: NCT03905460) https://clinicaltrials.gov/ct2/show/study/NCT03905460?term=NCT03905460&cond=Dyspnea&cntry=DK&draw=2&rank=1.
Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study
Authors: Coupland Lucy A. , Rabbolini David J. , Schoenecker Jonathan G. , Crispin Philip J. , Miller Jennene J. , Ghent Tony , Medcalf Robert L. , Aneman Anders E. 
Published: February 2023

Abstract
Background
Fibrinolysisis is essential for vascular blood flow maintenance and is triggered by endothelial and platelet release of tissue plasminogen activator (t-PA). In certain critical conditions, e.g. sepsis, acute respiratory failure (ARF) and trauma, the fibrinolytic response is reduced and may lead to widespread thrombosis and multi-organ failure. The mechanisms underpinning fibrinolysis resistance include reduced t-PA expression and/or release, reduced t-PA and/or plasmin effect due to elevated inhibitor levels, increased consumption and/or clearance. This study in critically ill patients with fibrinolysis resistance aimed to evaluate the ability of t-PA and plasminogen supplementation to restore fibrinolysis with assessment using point-of-care ClotPro viscoelastic testing (VET).

Methods
In prospective, observational studies, whole-blood ClotPro VET evaluation was carried out in 105 critically ill patients. In 32 of 58 patients identified as fibrinolysis-resistant (clot lysis time > 300 s on the TPA-test: tissue factor activated coagulation with t-PA accelerated fibrinolysis), consecutive experimental whole-blood VET was carried out with repeat TPA-tests spiked with additional t-PA and/or plasminogen and the effect on lysis time determined. In an interventional study in a patient with ARF and fibrinolysis resistance, the impact of a 24 h intravenous low-dose alteplase infusion on coagulation and fibrinolysis was prospectively monitored using standard ClotPro VET.

Results
Distinct response groups emerged in the ex vivo experimental VET, with increased fibrinolysis observed following supplementation with (i) t-PA only or (ii) plasminogen and t-PA. A baseline TPA-test lysis time of > 1000 s was associated with the latter group. In the interventional study, a gradual reduction (25%) in serial TPA-test lysis times was observed during the 24 h low-dose alteplase infusion.

Conclusions
ClotPro viscoelastic testing, the associated TPA-test and the novel experimental assays may be utilised to (i) investigate the potential mechanisms of fibrinolysis resistance, (ii) guide corrective treatment and (iii) monitor in real-time the treatment effect. Such a precision medicine and personalised treatment approach to the management of fibrinolysis resistance has the potential to increase treatment benefit, while minimising adverse events in critically ill patients.
Trial registration: VETtiPAT-ARF, a clinical trial evaluating ClotPro-guided t-PA (alteplase) administration in fibrinolysis-resistant patients with ARF, is ongoing (ClinicalTrials.gov NCT05540834; retrospectively registered September 15th 2022).
COVID-19 does not influence functional status after ARDS therapy
Authors: Bernard Alice , Serna-Higuita Lina Maria , Martus Peter , Mirakaj Valbona , Koeppen Michael , Zarbock Alexander , Marx Gernot , Putensen Christian , Rosenberger Peter , Haeberle Helene Anna 
Published: February 2023

Abstract
Rationale
Health-related quality of life after surviving acute respiratory distress syndrome has come into focus in recent years, especially during the coronavirus disease 2019 pandemic.

Objectives
A total of 144 patients with acute respiratory distress syndrome caused by COVID-19 or of other origin were recruited in a randomized multicenter trial.

Methods
Clinical data during intensive care treatment and data up to 180 days after study inclusion were collected. Changes in the Sequential Organ Failure Assessment score were used to quantify disease severity. Disability was assessed using the Barthel index on days 1, 28, 90, and 180.

Measurements
Mortality rate and morbidity after 180 days were compared between patients with and without COVID-19. Independent risk factors associated with high disability were identified using a binary logistic regression.

Main results
The SOFA score at day 5 was an independent risk factor for high disability in both groups, and score dynamic within the first 5 days significantly impacted disability in the non-COVID group. Mortality after 180 days and impairment measured by the Barthel index did not differ between patients with and without COVID-19.

Conclusions
Resolution of organ dysfunction within the first 5 days significantly impacts long-term morbidity. Acute respiratory distress syndrome caused by COVID-19 was not associated with increased mortality or morbidity.