bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertonicity induces mitochondrial extracellular vesicles (MEVs) that activate TNF-α and β-catenin signaling to promote adipocyte dedifferentiation
Authors: Liu Guopan , Wang Ying , Pan Yilin , Tian Li , Choi Ming Ho , Wang Li , Kim Jin Young , Zhang Jian , Cheng Shuk Han , Zhang Liang 
Published: December 2023

Abstract
Background
Recent studies demonstrated that elevated osmolarity could induce adipocyte dedifferentiation, representing an appealing procedure to generate multipotent stem cells. Here we aim to elucidate the molecular mechanisms that underlie osmotic induction of adipocyte reprogramming.

Methods
To induce dedifferentiation, the 3T3-L1 or SVF adipocytes were cultured under the hypertonic pressure in 2% PEG 300 medium. Adipocyte dedifferentiation was monitored by aspect ratio measurement, Oil Red staining and qPCR to examine the morphology, lipid droplets, and specific genes of adipocytes, respectively. The osteogenic and chondrogenic re-differentiation capacities of dedifferentiated adipocytes were also examined. To investigate the mechanisms of the osmotic stress-induced dedifferentiation, extracellular vesicles (EVs) were collected from the reprograming cells, followed by proteomic and functional analyses. In addition, qPCR, ELISA, and TNF-α neutralizing antibody (20 ng/ml) was applied to examine the activation and effects of the TNF-α signaling. Furthermore, we also analyzed the Wnt signaling by assessing the activation of β-catenin and applying BML-284, an agonist of β-catenin.

Results
Hypertonic treatment induced dedifferentiation of both 3T3-L1 and the primary stromal vascular fraction (SVF) adipocytes, characterized by morphological and functional changes. Proteomic profiling revealed that hypertonicity induced extracellular vesicles (EVs) containing mitochondrial molecules including NDUFA9 and VDAC. Functionally, the mitochondrial EVs (MEVs) stimulated TNF-α signaling that activates Wnt-β-catenin signaling and adipocyte dedifferentiation. Neutralizing TNF-α inhibited hypertonic dedifferentiation of adipocytes. In addition, direct activation of Wnt-β-catenin signaling using BML-284 could efficiently induce adipocyte dedifferentiation while circumventing the apoptotic effect of the hypertonic treatment.

Conclusions
Hypertonicity prompts the adipocytes to release MEVs, which in turn enhances the secretion of TNF-α as a pro-inflammatory cytokine during the stress response. Importantly, TNF-α is essential for the activation of the Wnt/β-catenin signaling that drives adipocyte dedifferentiation. A caveat of the hypertonic treatment is apoptosis, which could be circumvented by direct activation of the Wnt/β-catenin signaling using BML-284.
An evaluation of an open access iPSC training course: “How to model interstitial lung disease using patient-derived iPSCs”
Authors: Schweikert Anja , Kenny Sarah , Oglesby Irene , Glasgow Arlene , de Santi Chiara , Gensch Ingrid , Lachmann Nico , Desroziers Tifenn , Fletcher Camille , Snijders Deborah , Nathan Nadia , Hurley Killian ,   COST Open-ILD Group Management Committee, Snijders Deborah , Schwerk Nicolaus , Lachmann Nico , Griese Matthias , O’Toole Daniel , Borie Raphael 
Published: December 2023

Abstract
Background
Interstitial lung diseases (ILD) are a group of rare lung diseases with severe outcomes. The COST Innovator Grant aims to establish a first-of-a-kind open-access Biorepository of patient-derived induced pluripotent stem cells (iPSC) and to train researchers in the skills required to generate a robust preclinical model of ILD using these cells. This study aims to describe and evaluate the effectiveness of a training course designed to train researchers in iPSC techniques to model ILD.

Methods
74 researchers, physicians and stakeholders attended the training course in Dublin in May 2022 with 31 trainees receiving teaching in practical iPSC culturing skills. The training course learners were divided into the Hands-on (16 trainees) and Observer groups (15 trainees), with the Observers attending a supervised live-streamed experience of the laboratories skills directly delivered to the Hands-on group. All participants were asked to participate in an evaluation to analyse their satisfaction and knowledge gained during the Training Course, with means compared using t-tests.

Results
The gender balance in both groups was predominantly females (77.4%). The Hands-on group consisted mainly of researchers (75%), whereas all participants of the Observer group described themselves as clinicians. All participants in the Hands-on group were at least very satisfied with the training course compared to 70% of the participants in the Observer group. The knowledge assessment showed that the Hands-on group retained significantly more knowledge of iPSC characteristics and culturing techniques compared to the Observers (* < 0.05; p = 0.0457). A comprehensive learning video detailing iPSC culturing techniques was produced and is included with this manuscript.

Conclusions
The majority of participants were highly or very satisfied with the training course and retained significant knowledge about iPSC characteristics and culturing techniques after attending the training course. Overall, our findings demonstrate the feasibility of running hybrid Hands-on and Observer teaching events and underscore the importance of this type of training programme to appeal to a broad spectrum of interested clinicians and researchers particularly in rare disease. The long-term implications of this type of training event requires further study to determine its efficacy and impact on adoption of iPSC disease modelling techniques in participants’ laboratories.
Exploring distinct properties of endometrial stem cells through advanced single-cell analysis platforms
Authors: Lee Jin Woo , Lee Hwa-Yong 
Published: December 2023

AbstractThe endometrium is a dynamic tissue that undergoes cyclic changes in response to ovarian hormones during the menstrual cycle. These changes are crucial for pregnancy establishment and maintenance. Endometrial stem cells play a pivotal role in endometrial regeneration and repair by differentiating into various cell types within the endometrium. However, their involvement in endometrial disorders such as endometriosis, infertility, and endometrial cancer is still not fully understood yet. Traditional bulk sequencing methods have limitations in capturing heterogeneity and complexity of endometrial stem cell populations. To overcome these limitations, recent single-cell analysis techniques, including single-cell RNA sequencing (scRNA-Seq), single-cell ATAC sequencing (scATAC-Seq), and spatial transcriptomics, have emerged as valuable tools for studying endometrial stem cells. In this review, although there are still many technical limitations that require improvement, we will summarize the current state-of-the-art single-cell analysis techniques for endometrial stem cells and explore their relevance to related diseases. We will discuss studies utilizing various single-cell analysis platforms to identify and characterize distinct endometrial stem cell populations and investigate their dynamic changes in gene expression and epigenetic patterns during menstrual cycle and differentiation processes. These techniques enable the identification of rare cell populations, capture heterogeneity of cell populations within the endometrium, and provide potential targets for more effective therapies.
Pendelluft in hypoxemic patients resuming spontaneous breathing: proportional modes versus pressure support ventilation
Authors: Arellano Daniel H. , Brito Roberto , Morais Caio C. A. , Ruiz-Rudolph Pablo , Gajardo Abraham I. J. , Guiñez Dannette V. , Lazo Marioli T. , Ramirez Ivan , Rojas Verónica A. , Cerda María A. , Medel Juan N. , Illanes Victor , Estuardo Nivia R. , Bruhn Alejandro R. , Brochard Laurent J. , Amato Marcelo B. P. , Cornejo Rodrigo A. 
Published: December 2023

Abstract
Background
Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient’s respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS).

Methods
Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔPes100 ms]) and inspiratory effort (as the esophageal pressure–time product per minute [PTPmin]). We performed repeated measures analysis with post-hoc tests and mixed-effects models.

Results
Twenty patients mechanically ventilated for 9 [5–14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔPes 100 ms of –2.8 [−3.8–−1.9] cm H2O, −3.6 [−3.9–−2.4] cm H2O and −2.1 [−2.5–−1.1] cm H2O, respectively, p < 0.001 for both comparisons; PTPmin of 155 [118–209] cm H2O s/min, 197 [145–269] cm H2O s/min, and 134 [93–169] cm H2O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (β = -2.771, p-value < 0.001) and inspiratory effort (β = 0.026, p  < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTPmin (β = 2.606, p = 0.010 for NAVA, and β = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (β = 2.643, p = 0.009 for PAV +).

Conclusions
Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV.
Individual response in patient’s effort and driving pressure to variations in assistance during pressure support ventilation
Authors: Docci Mattia , Rezoagli Emanuele , Teggia-Droghi Maddalena , Coppadoro Andrea , Pozzi Matteo , Grassi Alice , Bianchi Isabella , Foti Giuseppe , Bellani Giacomo 
Published: December 2023

Abstract
Background
During Pressure Support Ventilation (PSV) an inspiratory hold allows to measure plateau pressure (Pplat), driving pressure (∆P), respiratory system compliance (Crs) and pressure-muscle-index (PMI), an index of inspiratory effort. This study aims [1] to assess systematically how patient’s effort (estimated with PMI), ∆P and tidal volume (Vt) change in response to variations in PSV and [2] to confirm the robustness of Crs measurement during PSV.

Methods
18 patients recovering from acute respiratory failure and ventilated by PSV were cross-randomized to four steps of assistance above (+ 3 and + 6 cmH2O) and below (-3 and -6 cmH2O) clinically set PS. Inspiratory and expiratory holds were performed to measure Pplat, PMI, ∆P, Vt, Crs, P0.1 and occluded inspiratory airway pressure (Pocc). Electromyography of respiratory muscles was monitored noninvasively from body surface (sEMG).

Results
As PSV was decreased, Pplat (from 20.5 ± 3.3 cmH2O to 16.7 ± 2.9, P < 0.001) and ∆P (from 12.5 ± 2.3 to 8.6 ± 2.3 cmH2O, P < 0.001) decreased much less than peak airway pressure did (from 21.7 ± 3.8 to 9.7 ± 3.8 cmH2O, P < 0.001), given the progressive increase of patient’s effort (PMI from -1.2 ± 2.3 to 6.4 ± 3.2 cmH2O) in line with sEMG of the diaphragm (r = 0.614; P < 0.001). As ∆P increased linearly with Vt, Crs did not change through steps (P = 0.119).

Conclusion
Patients react to a decrease in PSV by increasing inspiratory effort—as estimated by PMI—keeping Vt and ∆P on a desired value, therefore, limiting the clinician’s ability to modulate them. PMI appears a valuable index to assess the point of ventilatory overassistance when patients lose control over Vt like in a pressure-control mode. The measurement of Crs in PSV is constant—likely suggesting reliability—independently from the level of assistance and patient’s effort.
Security strategy for autonomous vehicle cyber-physical systems using transfer learning
Authors: Alsulami Abdulaziz A. , Al-Haija Qasem Abu , Alturki Badraddin , Alqahtani Ali , Alsini Raed 
Published: December 2023

AbstractCyber-physical systems (CPSs) are emergent systems that enable effective real-time communication and collaboration (C&C) of physical components such as control systems, sensors, actuators, and the surrounding environment through a cyber communication infrastructure. As such, autonomous vehicles (AVs) are one of the fields that have significantly adopted the CPS approach to improving people's lives in smart cities by reducing energy consumption and air pollution. Therefore, autonomous vehicle-cyber physical systems (AV-CPSs) have attracted enormous investments from major corporations and are projected to be widely used. However, AV-CPS is vulnerable to cyber and physical threat vectors due to the deep integration of information technology (IT), including cloud computing, with the communication process. Cloud computing is critical in providing the scalable infrastructure required for real-time data processing, storage, and analysis in AV-CPS, allowing these systems to work seamlessly in smart cities. CPS components such as sensors and control systems through network infrastructure are particularly vulnerable to cyber-attacks targeted by attackers using the communication system. This paper proposes an intelligent intrusion detection system (IIDS) for AV-CPS using transfer learning to identify cyberattacks launched against connected physical components of AVs through a network infrastructure. First, AV-CPS was developed by implementing the controller area network (CAN) and integrating it into the AV simulation model. Second, the dataset was generated from the AV-CPS. The collected dataset was then preprocessed to be trained and tested via pre-trained CNNs. Third, eight pre-trained networks were implemented, namely, InceptionV3, ResNet-50, ShuffleNet, MobileNetV2, GoogLeNet, ResNet-18, SqueezeNet, and AlexNet. The performance of the implemented models was evaluated. According to the experimental evaluation results, GoogLeNet outperformed all other pre-rained networks, scoring an F1- score of 99.47%.
What’s next in hospital digitization? A Delphi-based scenario study
Authors: Koebe Philipp , Bohnet-Joschko Sabine 
Published: December 2023

AbstractThe digital transformation has induced significant social and economic changes, impacting services of general interest, including healthcare. National healthcare systems serve as crucial pillars of social and prosperity security, necessitating adaptation in the face of digital transformation. Among healthcare institutions, hospitals play a vital role due to the nature and scope of their care services. This study presents a scenario-based investigation to explore the forthcoming changes in the healthcare environment and their potential effects on inpatient care. The study employed an iterative approach, commencing with an exploratory survey of experts to identify impact areas and descriptors. Subsequently, a two-round Delphi survey, involving a four-member stakeholder expert group, was conducted to evaluate and refine the identified parameters. A fuzzy clustering algorithm was utilized in the study to derive four different scenarios. These scenarios elucidate alternative development paths and describe the characteristics that may lead to these developments. The study’s findings offer valuable insights for formulating proactive recommendations and interventions to effectively address future developments in healthcare.
Pathways from media attention and peer communication to body dissatisfaction: the moderating role of protective filtering
Authors: Ji Jing , Xiang Xiaoli , Chen Ren , Chen Zenghong , Yan Jing 
Published: December 2023

Abstract
Background
Negative body image is a common psychological phenomenon among young Chinese women, and merits further investigation. Peers and the media are important factors that associated with body image. This study explored how media and peers promote body dissatisfaction among young Chinese women, including the mediating role of body surveillance and the moderating role of protective filtering.

Methods
3499 women from the general China community aged 18–40 years (M = 23.44 years, SD = 1.18 years) were investigated with sociocultural attitudes towards appearance scale-3, objectified body consciousness scale and protective filtering scale. The data were analyzed by using a moderated mediation model with SPSS and the Process 4.0 macro.

Results
Correlational analysis results indicated that body surveillance acted as a chained indirect effect between the internalization of media information and body dissatisfaction, as well as between peer comparison and body dissatisfaction. Moreover, protective filtering was demonstrated to moderate the path of media attention affecting the internalization of media information and the path of peer communication affecting peer comparisons.

Conclusion
Our results contribute to the understanding of the sociocultural mechanisms underlying young women’s negative body image. Furthermore, investigating the moderating effect of protective filtering is conducive to guiding future female positive body image interventions.
Addition of progesterone to feminizing gender-affirming hormone therapy in transgender individuals for breast development: a randomized controlled trial
Authors: Dijkman Benthe A.M. , Helder Danithsia , Boogers Lidewij S. , Gieles Noor C. , van Heesewijk Jason O. , Slaa Sjoerd te , Liberton Niels P.T.J. , Wiepjes Chantal M. , de Blok Christel J.M. , den Heijer Martin , Dreijerink Koen M.A. 
Published: December 2023

Abstract
Background
Feminizing gender-affirming hormone therapy (GAHT) for transgender individuals traditionally includes estradiol and androgen deprivation. Research has demonstrated that breast size as a result of GAHT in transgender women is often limited. Therefore, transgender women often choose to undergo breast augmentation surgery. Progesterone is important for breast development in cisgender women during puberty. A potential role for progesterone in breast development in transgender women has not been investigated in a randomized controlled experimental set-up. The primary objective of this study is to explore the effects on breast volume of addition of oral progesterone to GAHT with estradiol in transgender women after vaginoplasty or orchiectomy. Secondary objectives include assessment of safety, satisfaction, mood, sleep and sexual pleasure.

Methods
This is a non-blinded, non-placebo, randomized controlled trial using a factorial design in adult transgender individuals assigned male sex at birth who have undergone GAHT for at least one year and underwent vaginoplasty or orchiectomy. The study design allows for rapid assessment of potential synergistic effects of various dose combinations of estradiol and progesterone on breast volume change: Ninety participants will be randomized into six groups of 15 subjects each, receiving either the baseline dose of estradiol, the baseline dose of estradiol and progesterone 200 mg daily, the baseline dose of estradiol and progesterone 400 mg daily, twice the baseline dose of estradiol, twice the baseline dose of estradiol and progesterone 200 mg daily or twice the baseline dose of estradiol and progesterone 400 mg daily, all for a duration of 12 months. The main study parameters include changes in breast volume as determined by 3D measurements. Participants will be followed-up with laboratory testing including serum progesterone concentrations as well as surveys for satisfaction, mood, sleep quality and sexual pleasure.

Discussion
This study will indicate whether progesterone is safe and of additional value with regard to breast volume change in transgender individuals receiving feminizing GAHT. The results of this study will be useful for innovation of feminizing GAHT.

Trial registration
WHO International Clinical Trials Registry Platform: EUCTR2020-001952-16-NL; date of registration: 12 December 2020 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-001952-16-NL.
A model of hemodialysis after acute kidney injury in rats
Authors: Mallet J. , Billiet P.-A. , Scarton M. , Benichou N. , Bobot M. , Chaibi K. , Hertig A. , Hadchouel J. , Dreyfuss D. , Gaudry S. , Placier S. 
Published: December 2023

Abstract
Background
Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance.

Methods
Eighteen Sprague–Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent.

Results
After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7–46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2–33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1–191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2–140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7–250.3 µg).

Conclusions
This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.