bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of urgent start dialysis in a chronic kidney disease cohort followed by nephrologists
Authors: Tachikart Amin , Vachey Clément , Vauchy Charline , Savet Caroline , Ducloux Didier , Courivaud Cécile 
Published: June 2023

Abstract
Background
The French Renal Epidemiology and Information Network (REIN) registry collect dialysis initiation context for each patient starting dialysis with a flawed definition of urgent start dialysis (USD). The main objective of this study was to identify factors associated with USD in patients regularly followed-up by a nephrologist using a classification of USD considering the preparation to renal replacement therapy.

Methods
This retrospective cohort study included adult patients who started dialysis between 2012 and 2018 in the Franche-Comté region of France after a minimum of two nephrology consultations. We classified dialysis initiation context as follows: USD for patients with no dialysis access (DA) created or planned, unplanned non urgent start dialysis (UNUSD) for patients starting with a recent or non-functional DA and planned start dialysis (PSD) for those starting with a functional and mature DA.

Results
Four hundred and sixty-five patients met inclusion criteria. According to REIN registry, 94 (20.3%) patients were urgent starters (US) whereas with our classification 80 (17.2%) and 73 (15.7%) where respectively US and unplanned non urgent starters (UNUS). The factors independently associated with USD in our classification were: stroke (odds ratio(OR) = 2.76, 95% confidence interval (95%CI)=[1.41–5.43]), cardiac failure (OR = 1.78, 95%CI=[1.07–2.96]) and the number of nephrology consultations prior dialysis onset (OR = 0.73, 95%CI=[0.64–0.83]). Thirty-one patients died during the first year after dialysis start. According to our classification, we observed significantly different survival probabilities: 95.7%, 89.5% and 83.4% respectively for planned starters, UNUS and US (p = 0.001).

Conclusion
The two factors independently associated with USD were cardiac failure and stroke.
A feasibility study for objective evaluation of visual acuity based on pattern-reversal visual evoked potentials and other related visual parameters with machine learning algorithm
Authors: Chen Jian Zheng , Li Cong Cong , Li Shao Heng , Su Yu Ting , Zhang Tao , Wang Yu Sheng , Dou Guo Rui , Chen Tao , Wang Xiao Cheng , Zhang Zuo Ming 
Published: June 2023

Abstract
Background
To develop machine learning models for objectively evaluating visual acuity (VA) based on pattern-reversal visual evoked potentials (PRVEPs) and other related visual parameters.

Methods
Twenty-four volunteers were recruited and forty-eight eyes were divided into four groups of 1.0, 0.8, 0.6, and 0.4 (decimal vision). The relationship between VA, peak time, or amplitude of P100 recorded at 5.7°, 2.6°, 1°, 34′, 15′, and 7′ check sizes were analyzed using repeated-measures analysis of variance. Correlations between VA and P100, contrast sensitivity (CS), refractive error, wavefront aberrations, and visual field were analyzed by rank correlation. Based on meaningful P100 peak time, P100 amplitude, and other related visual parameters, four machine learning algorithms and an ensemble classification algorithm were used to construct objective assessment models for VA. Receiver operating characteristic (ROC) curves were used to compare the efficacy of different models by repeated sampling comparisons and ten-fold cross-validation.

Results
The main effects of P100 peak time and amplitude between different VA and check sizes were statistically significant (all P < 0.05). Except amplitude at 2.6° and 5.7°, VA was negatively correlated with peak time and positively correlated with amplitude. The peak time initially shortened with increasing check size and gradually lengthened after the minimum value was reached at 1°. At the 1° check size, there were statistically significant differences when comparing the peak times between the vision groups with each other (all P < 0.05), and the amplitudes of the vision reduction groups were significantly lower than that of the 1.0 vision group (all P < 0.01). The correlations between peak time, amplitude, and visual acuity were all highest at 1° (rs = − 0.740, 0.438). VA positively correlated with CS and spherical equivalent (all P < 0.001). There was a negative correlation between VA and coma aberrations (P < 0.05). For different binarization classifications of VA, the classifier models with the best assessment efficacy all had the mean area under the ROC curves (AUC) above 0.95 for 500 replicate samples and above 0.84 for ten-fold cross-validation.

Conclusions
Machine learning models established by meaning visual parameters related to visual acuity can assist in the objective evaluation of VA.
Macrophage PTEN controls STING-induced inflammation and necroptosis through NICD/NRF2 signaling in APAP-induced liver injury
Authors: Yang Tao , Qu Xiaoye , Zhao Jiaying , Wang Xiao , Wang Qian , Dai Jingjing , Zhu Chuanlong , Li Jun , Jiang Longfeng 
Published: June 2023

Abstract
Background
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling has been known to play a critical role in maintaining cellular and tissue homeostasis, which also has an essential role in the inflammatory response. However, it remains unidentified whether and how the macrophage PTEN may govern the innate immune signaling stimulator of interferon genes (STING) mediated inflammation and hepatocyte necroptosis in APAP-induced liver injury (AILI).

Methods
Myeloid-specific PTEN knockout (PTENM−KO) and floxed PTEN (PTENFL/FL) mice were treated with APAP (400 mg/kg) or PBS. In a parallel in vitro study, bone marrow-derived macrophages (BMMs) were isolated from these conditional knockout mice and transfected with CRISPR/Cas9-mediated Notch1 knockout (KO) or CRISPR/Cas9-mediated STING activation vector followed by LPS (100 ng/ml) stimulation.

Results
Here, we report that myeloid-specific PTEN knockout (PTENM−KO) mice were resistant to oxidative stress-induced hepatocellular injury with reduced macrophage/neutrophil accumulation and proinflammatory mediators in AILI. PTENM−KO increased the interaction of nuclear Notch intracellular domain (NICD) and nuclear factor (erythroid-derived 2)-like 2 (NRF2) in the macrophage nucleus, reducing reactive oxygen species (ROS) generation. Mechanistically, it is worth noting that macrophage NICD and NRF2 co-localize within the nucleus under inflammatory conditions. Additionally, Notch1 promotes the interaction of immunoglobulin kappa J region (RBPjκ) with NRF2. Disruption of the Notch1 signal in PTEN deletion macrophages, reduced RBPjκ and NRF2 binding, and activated STING signaling. Moreover, PTENM−KO macrophages with STING activated led to ROS generation and TNF-α release, resulting in hepatocyte necroptosis upon co-culture with primary hepatocytes.

Conclusions
Our findings demonstrate that the macrophage PTEN-NICD/NRF2-STING axis is critical to regulating oxidative stress-induced liver inflammation and necroptosis in AILI and implies the therapeutic potential for managing sterile liver inflammation.

Graphical Abstract
Enpp1 deficiency caused chondrocyte apoptosis by inhibiting AMPK signaling pathway
Authors: Gao Zhiqiang , Wang Qiang , Guo Kai , Li Xinhua , Huang Yufeng 
Published: June 2023

Abstract
Objective and background
The deficiency of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) causes the phenotype similar to knee osteoarthritis (OA). However, the molecular mechanism is poorly understood.

Method
The global deletion of Enpp1 (Enpp1−/−) mice was created to analyze the role of Enpp1 in the progress of knee OA. The apoptosis, proliferation and chondrogenic differentiation ability of chondrocytes from wild-type (WT) and Enpp1−/− joints were compared. According to the results of high-throughput quantitative molecular measurements, the proteins of chondrocytes from WT and Enpp1−/− mice were used to explore the mechanism of Enpp1 deficiency-associated knee OA.

Result
In Enpp1−/− knee joints, we found significant chondrocyte apoptosis and proteomic results showed that abnormal expression of AMP-activated protein kinase (AMPK) signaling pathway may contribute to this phenotype. In primary chondrocyte cultures in vitro, Enpp1 deletion dramatically enhancing chondrocyte apoptosis. Meanwhile, we found Enpp1 deletion inhibits the phosphorylation of AMPK (P-AMPK). We also found that decreased level of P-AMPK and chondrocyte apoptosis, which are caused by Enpp1 deficiency, can be reversed by Acadesine (AICAR), the activator of AMPK.

Conclusion
Consequently, Enpp1 deficiency plays an essential role in knee OA by regulating AMPK signaling pathway.
Formononetin alleviates acute pancreatitis by reducing oxidative stress and modulating intestinal barrier
Authors: Yang Jun , Sha Xiaowei , Wu Di , Wu Bo , Pan Xiaohua , Pan Li-Long , Gu Yuanlong , Dong Xiaoliang 
Published: June 2023

Abstract
Background
Acute pancreatitis (AP) is a recurrent inflammatory disease. Studies have shown that intestinal homeostasis is essential for the treatment of AP. Formononetin is a plant-derived isoflavone with antioxidant properties that can effectively treat a variety of inflammatory diseases. This study aims to investigate the role of formononetin in protecting against AP and underlying mechanism.

Methods
Caerulein was used to induce AP. The inflammatory cytokines were detected using Quantitative real-time PCR and commercial kits. Histological examination was applied with hematoxylin and eosin staining. Western blot was conducted to detect expression of intestinal barrier protein and signaling molecular. Molecular docking was performed to assess protein-ligand interaction.

Results
In this study, we found formononetin administration significantly reduced pancreatic edema, the activities of serum amylase, lipase, myeloperoxidase, and serum endotoxin. The mRNA levels of inflammatory cytokines such as tumor necrosis factor α, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta (IL-1β) in pancreas were also significantly decreased by formononetin. The following data showed formononetin pretreatment up-regulated the expressions of tight junction proteins in the colon, and decreased Escherichia coli translocation in the pancreas. In addition, formononetin inhibited the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 in pancreatic and colonic tissues of AP mice. Moreover, formononetin activated Kelch Like ECH Associated Protein 1 (Keap1) / Nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway to reduce reactive oxygen species (ROS) levels. Docking results showed that formononetin interact with Keap1 through hydrogen bond.

Conclusions
These findings demonstrate that formononetin administration significantly mitigate AP through reducing oxidative stress and restoring intestinal homeostasis, and provide insights into the new treatment for AP.
Prevalence, reasons, and timing of decisions to withhold/withdraw life-sustaining therapy for out-of-hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation
Authors: Naito Hiromichi , Sakuraya Masaaki , Hongo Takashi , Takada Hiroaki , Yumoto Tetsuya , Yorifuji Takashi , Hifumi Toru , Inoue Akihiko , Sakamoto Tetsuya , Kuroda Yasuhiro , Nakao Atsunori ,   SAVE-J II Study Group
Published: June 2023

Abstract
Background
Extracorporeal cardiopulmonary resuscitation (ECPR) is rapidly becoming a common treatment strategy for patients with refractory cardiac arrest. Despite its benefits, ECPR raises a variety of ethical concerns when the treatment is discontinued. There is little information about the decision to withhold/withdraw life-sustaining therapy (WLST) for out-of-hospital cardiac arrest (OHCA) patients after ECPR.

Methods
We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter study of ECPR in Japan. Adult patients who underwent ECPR for OHCA with medical causes were included. The prevalence, reasons, and timing of WLST decisions were recorded. Outcomes of patients with or without WLST decisions were compared. Further, factors associated with WLST decisions were examined.

Results
We included 1660 patients in the analysis; 510 (30.7%) had WLST decisions. The number of WLST decisions was the highest on the first day and WSLT decisions were made a median of two days after ICU admission. Reasons for WLST were perceived unfavorable neurological prognosis (300/510 [58.8%]), perceived unfavorable cardiac/pulmonary prognosis (105/510 [20.5%]), inability to maintain extracorporeal cardiopulmonary support (71/510 [13.9%]), complications (10/510 [1.9%]), exacerbation of comorbidity before cardiac arrest (7/510 [1.3%]), and others. Patients with WLST had lower 30-day survival (WLST vs. no-WLST: 36/506 [7.1%] vs. 386/1140 [33.8%], p < 0.001). Primary cerebral disorders as cause of cardiac arrest and higher severity of illness at intensive care unit admission were associated with WLST decisions.

Conclusion
For approximately one-third of ECPR/OHCA patients, WLST was decided during admission, mainly because of perceived unfavorable neurological prognoses. Decisions and neurological assessments for ECPR/OHCA patients need further analysis.
The MTego trap: a potential tool for monitoring malaria and arbovirus vectors
Authors: Maasayi Masudi Suleiman , Machange Jane Johnson , Kamande Dismas S. , Kibondo Ummi Abdul , Odufuwa Olukayode G. , Moore Sarah Jane , Tambwe Mgeni Mohamed 
Published: June 2023

Abstract
Background
Odour-baited traps are useful for vector surveillance and control. However, most existing traps have shown inconsistent recapture rates across different mosquito species, necessitating the need for more effective and efficient traps. The MTego trap with integrated thermal stimuli has been developed as an alternative trap. This study was undertaken to determine and compare the efficacy of the MTego trap to that of the Biogents (BG) modular BG-Pro (BGP) trap for sampling different mosquito species in a semi-field system.

Methods
Fully balanced Latin square design experiments (no-choice and dual choice) were conducted in semi-field chambers using laboratory-reared female Anopheles gambiae sensu stricto, Anopheles funestus, Anopheles arabiensis, Culex quinquefasciatus and Aedes aegypti. There were 16 replicates, and 50 mosquitoes of each species were released in each chamber per replicate. The evaluated traps were as follows: the MTego trap baited with PM6 (MT-PM6), the MTego trap baited with BG-Lure (BGL) (MT-BGL), and the BGP trap baited with BG-Lure (BGP-BGL).

Results
In the no-choice test, the MT-BGL and BGP-BGL traps captured a similar proportion of An. gambiae (31% vs 29%, P-value = 0.519) and An. funestus (32% vs 33%, P = 0.520). The MT-PM6 and BGP-BGL traps showed no significant difference in capturing Ae. aegypti (33% vs 31%, P = 0.324). However, the BGP-BGL caught more An. arabiensis and Cx. quinquefasciatus mosquitoes than the other traps (P < 0.0001). In the dual-choice test of MT-PM6 vs BGP-BGL, similar proportions of An. funestus (25% vs 27%, P = 0.473) and Ae. aegypti (29% vs 25%, P = 0.264) were captured in the traps, while the BGP-BGL captured more An. gambiae, An. arabiensis and Cx. quinquefasciatus mosquitoes than the MT-PM6 (P < 0.0001).

Conclusions
This study demonstrated that the MTego trap has potential as a tool that can be used interchangeably with the BGP trap for sampling anthropophilic mosquitoes including African malaria vectors An. gambiae and An. funestus and the principal arbovirus vector Ae. aegypti.

Graphical abstract
Effect of positive airway pressure compliance on laryngopharyngeal reflux in obstructive sleep apnea patients
Authors: Tawaranurak Krongthong , Werathammo Methini 
Published: June 2023

Abstract
Objectives
To determine the effect of continuous positive airway pressure (CPAP) compliance on symptoms and signs of laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea (OSA).

Results
Thirty patients were included. The participants were divided into good compliance (n = 21) and poor compliance (n = 9) groups. After 6-month CPAP treatment, the reflux symptom index score significantly decreased in both the good compliance group (20 (17,24) vs. 14 (10,18), p < 0.001) and the poor compliance group (21 (18,25) vs. 10 (5,16), p < 0.05). Reflux finding score was significantly reduced in both the good compliance group (8 (6,9) vs. 4 (3,5), p < 0.001) and the poor compliance group (6 (4,8) vs. 3 (2,4), p < 0.05). However, there were no statistically significant differences between the groups. CPAP treatment reduces the symptoms and signs of LPR. However, CPAP compliance does not correlate with improvement in LPR in patients with OSA.
A multicomponent complex intervention for supportive follow-up of persons with chronic heart failure: a randomized controlled pilot study (the UTILE project)
Authors: Schäfer-Keller Petra , Graf Denis , Denhaerynck Kris , Santos Gabrielle Cécile , Girard Josepha , Verga Marie-Elise , Tschann Kelly , Menoud Grégoire , Kaufmann Anne-Laure , Leventhal Marcia , Richards David A. , Strömberg Anna 
Published: June 2023

Abstract
Background
Heart failure (HF) is a progressive disease associated with a high burden of symptoms, high morbidity and mortality, and low quality of life (QoL). This study aimed to evaluate the feasibility and potential outcomes of a novel multicomponent complex intervention, to inform a future full-scale randomized controlled trial (RCT) in Switzerland.

Methods
We conducted a pilot RCT at a secondary care hospital for people with HF hospitalized due to decompensated HF or with a history of HF decompensation over the past 6 months. We randomized 1:1; usual care for the control (CG) and intervention group (IG) who received the intervention as well as usual care. Feasibility measures included patient recruitment rate, study nurse time, study attrition, the number and duration of consultations, intervention acceptability and intervention fidelity. Patient-reported outcomes included HF-specific self-care and HF-related health status (KCCQ-12) at 3 months follow-up. Clinical outcomes were all-cause mortality, hospitalization and days spent in hospital.

Results
We recruited 60 persons with HF (age mean = 75.7 years, ± 8.9) over a 62-week period, requiring 1011 h of study nurse time. Recruitment rate was 46.15%; study attrition rate was 31.7%. Follow-up included 2.14 (mean, ± 0.97) visits per patient lasting a total of 166.96 min (mean, ± 72.55), and 3.1 (mean, ± 1.7) additional telephone contacts. Intervention acceptability was high. Mean intervention fidelity was 0.71. We found a 20-point difference in mean self-care management change from baseline to 3 months in favour of the IG (Cohens’ d = 0.59). Small effect sizes for KCCQ-12 variables; less IG participants worsened in health status compared to CG participants. Five deaths occurred (IG = 3, CG = 2). There were 13 (IG) and 18 (CG) all-cause hospital admissions; participants spent 8.90 (median, IQR = 9.70, IG) and 15.38 (median, IQR = 18.41, CG) days in hospital. A subsequent full-scale effectiveness trial would require 304 (for a mono-centric trial) and 751 participants (for a ten-centre trial) for HF-related QoL (effect size = 0.3; power = 0.80, alpha = 0.05).

Conclusion
We found the intervention, research methods and outcomes were feasible and acceptable. We propose increasing intervention fidelity strategies for a full-scale trial.

Trial registration
ISRCTN10151805, retrospectively registered 04/10/2019.
Regenerative capacity of trophoblast stem cell-derived extracellular vesicles on mesenchymal stem cells
Authors: Go Yoon-Young , Lee Chan-mi , Chae Sung-Won , Song Jae-Jun 
Published: June 2023

Abstract

Background
Human mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs.

Methods
We employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs.

Results
TSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway.

Conclusion
The results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.

Graphical abstract
Immunotherapy-induced thyroid dysfunction: an updated review
Authors: Baraka Bahaaeldin , Abosheaishaa Hazem , Nassar Mahmoud 
Published: June 2023

AbstractImmunotherapy medicines (immune checkpoint inhibitors, ICIs) that work directly on the immune system have shown vastly increased survival for people with cancer in phases 2 and 3 clinical studies during the past few years. Nevertheless, ICI treatment (irAEs) may trigger immune-related adverse effects. An underactive thyroid is among the most frequent endocrine irAE, affecting about 40% of individuals who received ICIs. Our review aims to collect and organize the most recent data on immunotherapy-induced thyroid dysfunction in cancer patients, including its prevalence, diagnostic criteria, and treatment options and to summarize those findings in a comprehensive review article. The incidence of irAEs varies depending on the type of cancer and the treatment regimen. Thyroid ultrasound, radioactive uptake scan, and PET CT scan can aid in diagnosing thyroid dysfunction. Thyroid dysfunction treatment necessitates collaboration between specialists in oncology, endocrinology, and primary care in a multidisciplinary team discussion. The prognosis of patients who suffered from thyroid dysfunction while on ICIs treatment is reasonably good. Suboptimal baseline thyroid function was linked with decreased overall survival (OS) among ICI-treated patients, but initiating replacement hormonal therapy after ICI initiation was associated with enhanced OS. More research work is required to identify these links and mechanisms of action.