bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss
Authors: Schlett Judith Stefanie , Mettang Melanie , Skaf Aladdin , Schweizer Pavel , Errerd Alina , Mulugeta Ephraim Alemayehu , Hein Tabea Melissa , Tsesmelis Konstantinos , Tsesmelis Miltiadis , Büttner Ulrike F. G. , Wendt Heinrich , Abaei Alireza , Rasche Volker , Prex Vivien , Nespoli Ester , Alami Najwa Ouali , Tews Daniel , Walther Paul , Yilmazer-Hanke Deniz , Oswald Franz , Dimou Leda , Wirth Thomas , Baumann Bernd 
Published: April 2023

Abstract
Background
Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic pro-inflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven by glia cells and associated with neurodegenerative processes. White matter degeneration (WMD), a well-known process in the aging brain, manifests in myelin loss finally resulting in motor, sensory and cognitive impairments. Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress. Yet, the immediate impact of chronic inflammatory stress like inflammaging on OL homeostasis, myelin maintenance and WMD remains open.

Methods
To functionally analyze the role of IKK/NF-κB signaling in the regulation of myelin homeostasis and maintenance in the adult CNS, we established a conditional mouse model allowing NF-κB activation in mature myelinating oligodendrocytes. IKK2-CAPLP−CreERT2 mice were characterized by biochemical, immunohistochemical, ultrastructural and behavioral analyses. Transcriptome data from isolated, primary OLs and microglia cells were explored by in silico pathway analysis and validated by complementary molecular approaches.

Results
Chronic NF-κB activation in mature OLs leads to aggravated neuroinflammatory conditions phenocopying brain inflammaging. As a consequence, IKK2-CAPLP−CreERT2 mice showed specific neurological deficits and impaired motoric learning. Upon aging, persistent NF-κB signaling promotes WMD in these mice as ultrastructural analysis revealed myelination deficits in the corpus callosum accompanied by impaired myelin protein expression. RNA-Seq analysis of primary oligodendrocytes and microglia cells uncovers gene expression signatures associated with activated stress responses and increased post mitotic cellular senescence (PoMiCS) which was confirmed by elevated senescence-associated β-galactosidase activity and SASP gene expression profile. We identified an elevated integrated stress response (ISR) characterized by phosphorylation of eIF2α as a relevant molecular mechanism which is able to affect translation of myelin proteins.

Conclusions
Our findings demonstrate an essential role of IKK/NF-κB signaling in mature, post-mitotic OLs in regulating stress-induced senescence in these cells. Moreover, our study identifies PoMICS as an important driving force of age-dependent WMD as well as of traumatic brain injury induced myelin defects.

Graphical Abstract
Emerging evidence and treatment paradigm of non-small cell lung cancer
Authors: Liu Si-Yang Maggie , Zheng Mei-Mei , Pan Yi , Liu Si-Yang , Li Yangqiu , Wu Yi-Long 
Published: April 2023

AbstractResearch on biomarker-driven therapy and immune check-point blockade in non-small cell lung cancer (NSCLC) is rapidly evolving. The width and depth of clinical trials have also dramatically improved in an unprecedented speed. The personalized treatment paradigm evolved every year. In this review, we summarize the promising agents that have shifted the treatment paradigm for NSCLC patients across all stages, including targeted therapy and immunotherapy using checkpoint inhibitors. Based on recent evidence, we propose treatment algorithms for NSCLC and propose several unsolved clinical issues, which are being explored in ongoing clinical trials. The results of these trials are likely to impact future clinical practice.
DeepEdit: single-molecule detection and phasing of A-to-I RNA editing events using nanopore direct RNA sequencing
Authors: Chen Longxian , Ou Liang , Jing Xinyun , Kong Yimeng , Xie Bingran , Zhang Niubing , Shi Han , Qin Hang , Li Xuan , Hao Pei 
Published: April 2023

AbstractSingle-molecule detection and phasing of A-to-I RNA editing events remain an unresolved problem. Long-read and PCR-free nanopore native RNA sequencing offers a great opportunity for direct RNA editing detection. Here, we develop a neural network model, DeepEdit, that not only recognizes A-to-I editing events in single reads of Oxford Nanopore direct RNA sequencing, but also resolves the phasing of RNA editing events on transcripts. We illustrate the robustness of DeepEdit by applying it toSchizosaccharomyces pombeandHomo sapienstranscriptome data. We anticipate DeepEdit to be a powerful tool for the study of RNA editing from a new perspective.
Postoperative awake prone position in geriatric patients with hip fractures: a protocol for a randomized controlled trial on the efficacy of postoperative prone position in reducing pulmonary complications and improving oxygenation
Authors: Gao Yu-cheng , Shi Liu , Zhang Yuan-wei , Gao Wang , Tian Xie , Cao Mu-min , Li Ying-juan , Chen Hui , Rui Yun-feng 
Published: April 2023

AbstractIntroductionPostoperative pulmonary complications (PPCs) are prevalent in geriatric patients with hip fractures. Low oxygen level is one of the most important risk factors for PPCs. Prone position has been proven efficacy in improving oxygenation and delaying the progress of pulmonary diseases, especially in patients with acute respiratory distress syndrome induced by multiple etiologies. The application of awake prone position (APP) has also attracted widespread attention in recent years. A randomized controlled trial (RCT) will be carried out to measure the effect of postoperative APP in a population of geriatric patients undergoing hip fracture surgery.MethodsThis is an RCT. Patients older than 65 years old admitted through the emergency department and diagnosed with an intertrochanteric or femoral neck fracture will be eligible for enrollment and assigned randomly to the control group with routine postoperative management of orthopedics or APP group with an additional prone position for the first three consecutive postoperative days (PODs). Patients receiving conservative treatment will not be eligible for enrollment. We will record the difference in the patient’s room-air-breathing arterial partial pressure of oxygen (PaO2) values between the 4thPOD (POD 4) and emergency visits, the morbidity of PPCs and other postoperative complications, and length of stay. The incidence of PPCs, readmission rates, and mortality rates will be followed up for 90 PODs.DiscussionWe describe the protocol for a single-center RCT that will evaluate the efficacy of postoperative APP treatment in reducing pulmonary complications and improving oxygenation in geriatric patients with hip fractures.Ethics and disseminationThis protocol was approved by the independent ethics committee (IEC) for Clinical Research of Zhongda Hospital, Affiliated to Southeast University, and is registered on the Chinese Clinical Trial Registry. The findings of the trial will be disseminated through peer-reviewed journals.Ethics approval number2021ZDSYLL203-P01Trial registrationChiCTRChiCTR2100049311. Registered on 29 July 2021.Trial statusRecruiting. Recruitment is expected to be completed in December 2024.
Associated factors of prosthetic rehabilitation in specialized dental care in Brazil: a cross-sectional study
Authors: da Cunha Inara Pereira , de Lacerda Valéria Rodrigues , Silva Manoelito Ferreira , Bomfim Rafael Aiello 
Published: April 2023

AbstractObjectiveThis study aimed to analyze the individual and contextual factors associated with prosthetic rehabilitation in Dental Specialty Centers (DSC) in Brazil. A cross-sectional study, with secondary data from modules II and III of the External Assessment of the 2nd Cycle of the National Program for the Improvement of Access and Quality (PMAQ) of DSCs, was conducted in 2018. Individual variables considered were socioeconomic conditions and perceptions about the structure and service of the DSC. Contextual variables were related to DSC. We considered the region of the country (capital or countryside), geographic location and work process of the DSC for prosthetic rehabilitation. The association between individual and contextual variables and prosthetic rehabilitation in the DSC was analyzed by multilevel logistic regression.ResultsTen thousand three hundred ninety-one users from 1,042 DSC participated. Of these, 24.4% used dental prosthesis and 26.0% performed at the DSC. In the final analysis, performed dental prostheses in the DSC individuals with less education (OR = 1.23; CI95%:1.01–1.50) and residents of the same city as the DSC (OR = 1.69; CI95%:1.07–2.66), at a contextual level, DSCs of the countryside (OR = 1.41; CI95%:1.01–1.97) were associated with the outcome. Individual and contextual factors were associated with prosthetic rehabilitation in the DSC.
Low-intensity pulsed ultrasound promotes mesenchymal stem cell transplantation-based articular cartilage regeneration via inhibiting the TNF signaling pathway
Authors: Chen Yiming , Yang Huiyi , Wang Zhaojie , Zhu Rongrong , Cheng Liming , Cheng Qian 
Published: April 2023

Abstract
Background
Mesenchymal stem cell (MSC) transplantation therapy is highly investigated for the regenerative repair of cartilage defects. Low-intensity pulsed ultrasound (LIPUS) has the potential to promote chondrogenic differentiation of MSCs. However, its underlying mechanism remains unclear. Here, we investigated the promoting effects and mechanisms underlying LIPUS stimulation on the chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further evaluated its regenerative application value in articular cartilage defects in rats.

Methods
LIPUS was applied to stimulate cultured hUC-MSCs and C28/I2 cells in vitro. Immunofluorescence staining, qPCR analysis, and transcriptome sequencing were used to detect mature cartilage-related markers of gene and protein expression for a comprehensive evaluation of differentiation. Injured articular cartilage rat models were established for further hUC-MSC transplantation and LIPUS stimulation in vivo. Histopathology and H&E staining were used to evaluate the repair effects of the injured articular cartilage with LIPUS stimulation.

Results
The results showed that LIPUS stimulation with specific parameters effectively promoted the expression of mature cartilage-related genes and proteins, inhibited TNF-α gene expression in hUC-MSCs, and exhibited anti-inflammation in C28/I2 cells. In addition, the articular cartilage defects of rats were significantly repaired after hUC-MSC transplantation and LIPUS stimulation.

Conclusions
Taken together, LIPUS stimulation could realize articular cartilage regeneration based on hUC-MSC transplantation due to the inhibition of the TNF signaling pathway, which is of clinical value for the relief of osteoarthritis.
Epitope mapping of the monoclonal antibody IP5B11 used for detection of viral haemorrhagic septicaemia virus facilitated by genome sequencing of carpione novirhabdovirus
Authors: Ito Takafumi , Mekata Tohru , Olesen Niels Jørgen , Lorenzen Niels 
Published: April 2023

AbstractThe monoclonal antibody (mAb) IP5B11, which is used worldwide for the diagnosis of viral haemorrhagic septicaemia (VHS) in fish, reacts with all genotypes of VHS virus (VHSV). The mAb exceptionally also reacts with the carpione rhabdovirus (CarRV). Following next generation genome sequencing of CarRV and N protein sequence alignment including five kinds of fish novirhabdoviruses, the epitope recognized by mAb IP5B11 was identified. Dot blot analysis confirmed the epitope of mAb IP5B11 to be associated with the region N219 to N233 of the N protein of VHSV. Phylogenetic analysis identified CarRV as a new member of the fish novirhabdoviruses.
Epidemiology of pediatric schistosomiasis in hard-to-reach areas and populations: a scoping review
Authors: Isaiah Phyllis Munyiva , Sólveig Palmeirim Marta , Steinmann Peter 
Published: April 2023

Abstract
Background
Schistosomiasis affects over 250 million people worldwide. Despite children and the poor being key risk groups, limited research and control activities target pre-school aged children (PSAC) and hard-to-reach populations. As endemic countries shift the goals of their schistosomiasis programs from morbidity control to disease elimination, there is a need for inclusive planning to cover all affected age groups from all geographical areas and populations to achieve sustainable impact and health equity.

Methods
We conducted searches in MEDLINE, Web of Science, Embase (Ovid), and LILACS per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews (PRISMA-ScR) guidelines. Quality assessment of identified articles was done using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. Relevant study data were extracted from the articles and entered into Microsoft Excel 2016 for descriptive analysis.

Results
From the 17,179 screened articles, we identified 13 eligible studies on schistosomiasis in PSAC living in hard-to-reach areas and populations. All identified studies were from sub-Saharan Africa. The mean sample size of the retained studies was 572, with a balanced sex distribution among the young children sampled in each study. Ten studies investigated Schistosoma mansoni, one investigated Schistosoma haematobium, while two covered both S. mansoni and S. haematobium in the target population. The prevalence of S. mansoni among PSAC in the included studies was estimated at 12.9% in Ghana, 80.3–90.5% in Kenya, 35.0% in Madagascar, 9.6–78.0% in Senegal, 11.2–35.4% in Sierra Leone, 44.4–54.9% in Tanzania and 39.3–74.9% in Uganda. Out of the three studies that investigated S. haematobium, the presence of the infection was reported in only one study carried out in Nigeria. Schistosome infections reported in nearly all studies included in this review were of light intensity. Only one study conducted in Nigeria documented visible hematuria in 17.7% of the PSAC studied.

Conclusions
The findings document the high prevalence of schistosomiasis among PSAC in hard-to-reach populations and underscore the need to consider this population subgroup when designing the expansion of preventive chemotherapy and schistosomiasis control activities.

Graphical Abstract
“Scanxiety” and a sense of control: the perspective of lung cancer survivors and their caregivers on follow-up - a qualitative study
Authors: Seibel Katharina , Sauer Barbara , Wagner Bernd , Becker Gerhild 
Published: April 2023

Abstract
Objectives
Lung cancer survivors often suffer from physical, emotional and social long-term effects of disease and treatment. Caregivers are also affected by the cancer diagnosis throughout the course of the disease and are frequently burdened by high levels of psychosocial stress. However, little is known about how follow-up care after the completed treatment phase can help to improve long-term quality of life. In the context of patient-centred cancer care, considering the survivors’ and caregivers’ perspectives is an important step toward improving care structures. We therefore explored how lung cancer survivors and their caregivers experience follow-up examinations and their possible psychosocial effects on everyday life in order to shed light on what support is helpful for improving their quality of life.

Material and Methods
25 survivors after curative lung cancer treatment and 17 caregivers underwent a face-to-face semi-structured, audio-recorded interview that was analysed using qualitative content analysis.

Results
Especially burdened cancer survivors and caregivers described recurring anxiety before a follow-up appointment influencing their everyday life. At the same time, follow-up care also provided reassurance of still being healthy and helped regain a sense of security and control until the following scan. Despite possible long-term consequences in everyday life, the interviewees reported that the survivors´ psychosocial needs were not explicitly assessed or discussed. Nevertheless, the interviewees indicated that conversations with the physician were important for the success of “good” follow-up care.

Conclusion
Anxiety surrounding follow-up scans, also known as “scanxiety”, is a common problem. In this study, we expanded on previous findings and found a positive aspect of scans, namely regaining a sense of security and control, which can strengthen the psychological well-being of the survivors and their families. To optimize follow-up care and improve the quality of life of lung cancer survivors and caregivers, strategies to integrate psychosocial care, like the introduction of survivorship care plans or increased use of patient-reported outcomes, should be explored in the future.
The moderating effect of emotion regulation in the association between social support and religiosity and psychological distress in adults
Authors: Karam Joya-Maria , Fekih-Romdhane Feten , Fawaz Mirna , Malaeb Diana , Obeid Sahar , Hallit Souheil 
Published: April 2023

Abstract
Background
Lebanese adults face daily obstacles due to their numerous responsibilities and non-ending external pressures to the extent that Lebanon has been ranked second among highest negative experiences countries worldwide. A sparse number of international studies showed that positive social support, religiosity and cognitive reappraisal would decrease psychological distress, but none in Lebanon. This study aimed to evaluate the association between social support, religiosity and psychological distress among Lebanese adults, taking into consideration the moderating role of emotion regulation.

Methods
387 adult participants enrolled in this cross-sectional study between May and July 2022. Participants were chosen from five different governorates in Lebanon, using the snowball sampling technique, and were asked to complete a structured questionnaire, which included the following scales: the Mature Religiosity Scale, the Emotional Regulation Scale, the Depression Anxiety Stress Scale, and the Multidimensional Scale of Perceived Social Support.

Results
The interaction social support by cognitive reappraisal was significantly associated with psychological distress; at high levels of cognitive reappraisal and low levels of expressive suppression, higher social support (Beta = − 0.07; p = .007) was significantly associated with lower psychological distress. The same was found at high levels of cognitive reappraisal and moderate levels of expressive suppression (Beta = − 0.08; p = .021). Social support alone was not significantly associated with psychological distress in the model (Beta = 0.15; t = 1.04; p = .300; 95% CI − 0.14; 0.44).

Conclusion
This cross-sectional study has provided evidence that the adequate use of emotional regulation skills such as high level of cognitive reappraisal and low level of expressive suppression with presence of social support would remarkably decrease psychological distress. This result casts a new light on clinical approaches to tackle this association between the emotional regulation of a patient in interpersonal psychotherapy.
Exploring the role of an IBT-based Informal teaching practice at an edutainment centre on pre-service English language teachers
Authors: Karacan Cemil Gökhan , Kesen Mutlu Aynur 
Published: April 2023

AbstractThe field experience in teacher education programs is limited to the formal teaching at assigned schools. However, there is a need for opportunities for pre-service teachers to practice teaching in other learning contexts. This multiple instrumental case study explored the role of an Inquiry-based Teaching-based informal teaching practice at an edutainment center on a group of 23 pre-service English language teachers. The data were collected through one-on-one semi-structured interviews, retrospective reflection papers and focus group interview. Findings showed that pre-service English language teachers gained valuable insights into different ways of managing the classroom and sustaining interaction with children. Furthermore, they increased their teacher awareness and became more autonomous teachers. The findings of this study have implications for teacher education program designers and teacher educators seeking to enhance the field experience of pre-service teachers.
Extracellular vesicles from immortalized mesenchymal stromal cells protect against neonatal hypoxic-ischemic brain injury
Authors: Labusek Nicole , Mouloud Yanis , Köster Christian , Diesterbeck Eva , Tertel Tobias , Wiek Constanze , Hanenberg Helmut , Horn Peter A. , Felderhoff-Müser Ursula , Bendix Ivo , Giebel Bernd , Herz Josephine 
Published: April 2023

Abstract

Background
Human mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) revealed neuroprotective potentials in various brain injury models, including neonatal encephalopathy caused by hypoxia–ischemia (HI). However, for clinical translation of an MSC-EV therapy, scaled manufacturing strategies are required, which is challenging with primary MSCs due to inter- and intra-donor heterogeneities. Therefore, we established a clonally expanded and immortalized human MSC line (ciMSC) and compared the neuroprotective potential of their EVs with EVs from primary MSCs in a murine model of HI-induced brain injury. In vivo activities of ciMSC-EVs were comprehensively characterized according to their proposed multimodal mechanisms of action.

Methods
Nine-day-old C57BL/6 mice were exposed to HI followed by repetitive intranasal delivery of primary MSC-EVs or ciMSC-EVs 1, 3, and 5 days after HI. Sham-operated animals served as healthy controls. To compare neuroprotective effects of both EV preparations, total and regional brain atrophy was assessed by cresyl-violet-staining 7 days after HI. Immunohistochemistry, western blot, and real-time PCR were performed to investigate neuroinflammatory and regenerative processes. The amount of peripheral inflammatory mediators was evaluated by multiplex analyses in serum samples.

Results
Intranasal delivery of ciMSC-EVs and primary MSC-EVs comparably protected neonatal mice from HI-induced brain tissue atrophy. Mechanistically, ciMSC-EV application reduced microglia activation and astrogliosis, endothelial activation, and leukocyte infiltration. These effects were associated with a downregulation of the pro-inflammatory cytokine IL-1 beta and an elevated expression of the anti-inflammatory cytokines IL-4 and TGF-beta in the brain, while concentrations of cytokines in the peripheral blood were not affected. ciMSC-EV-mediated anti-inflammatory effects in the brain were accompanied by an increased neural progenitor and endothelial cell proliferation, oligodendrocyte maturation, and neurotrophic growth factor expression.

Conclusion
Our data demonstrate that ciMSC-EVs conserve neuroprotective effects of primary MSC-EVs via inhibition of neuroinflammation and promotion of neuroregeneration. Since ciMSCs can overcome challenges associated with MSC heterogeneity, they appear as an ideal cell source for the scaled manufacturing of EV-based therapeutics to treat neonatal and possibly also adult brain injury.