bluuebunny/crossref_metadata_2025_split huggingface dataset:
“I can’t imagine having to do it on your own”: a qualitative study on postoperative transitions in care from the perspectives of older adults with frailty
Authors: Hladkowicz Emily , Auais Mohammad , Kidd Gurlavine , McIsaac Daniel I. , Miller Jordan 
Published: December 2023

Abstract
Background
Adults aged 65 and older have surgery more often than younger people and often live with frailty. The postoperative transition in care from hospital to home after surgey is a challenging time for older adults with frailty as they often experience negative outcomes. Improving postoperative transitions in care for older adults with frailty is a priority. However, little knowledge from the perspective of older adults with frailty is available to support meaningful improvements in postoperative transitions in care.

Objective
To explore what is important to older adults with frailty during a postoperative transition in care.

Methods
This qualitative study used an interpretive description methodology. Twelve adults aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery and could speak in English participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using thematic analysis.

Results
Five themes were constructed: 1) valuing going home after surgery; 2) feeling empowered through knowledge and resources; 3) focusing on medical and functional recovery; 4) informal caregivers and family members play multiple integral roles; and 5) feeling supported by healthcare providers through continuity of care. Each theme had 3 sub-themes.

Conclusion
Future programs should focus on supporting patients to return home by empowering patients with resources and clear communication, ensuring continuity of care, creating access to homecare and virtual support, focusing on functional and medical recovery, and recognizing the invaluable role of informal caregivers.
Vascular endothelial growth factor induces the migration of human airway smooth muscle cells by activating the RhoA/ROCK pathway
Authors: Lv Chengtian , Huang Yuwen , Yan Ruirong , Gao Yuanmei 
Published: December 2023

Abstract
Background
Airway remodeling due to increased airway smooth muscle cell (ASMC) mass, likely due to enhanced proliferation, hypertrophy, and migration, has been proven to be highly correlated with decreased lung function in asthma patients. Vascular endothelial growth factor (VEGF) mediates vascular and extravascular remodeling and inflammation and has been proven to be involved in the progression of asthma. Previous studies have focused on the effects of VEGF on ASMC proliferation, but few researchers have focused on the effects of VEGF on human ASMC migration. The purpose of this study was to explore the effect of VEGF on the migration of ASMCs and its related signaling pathway mechanism to provide evidence for the treatment of airway remodeling.

Methods
We examined the effects of VEGF induction on ASMC migration and explored the mechanisms involved in ASMC migration.

Results
We found by wound healing and Transwell assays that VEGF promoted ASMC migration. Through the Cell Counting Kit-8 (CCK-8) experiment, we found that VEGF had no significant effect on the proliferation of ASMCs, which excluded the involvement of cell proliferation in the process of wound healing. Moreover, a cellular immunofluorescence assay showed that VEGF promoted F-actin reorganization, and Western blotting showed that VEGF improved RhoA activation and myosin phosphatase targeting subunit-1 (MYPT1) and myosin light chain (MLC) phosphorylation in ASMCs. Treatment with the ROCK inhibitor Y27632 significantly attenuated the effects of VEGF on MYPT1/MLC activation and cell migration.

Conclusion
In conclusion, the results suggest that the promigratory function of VEGF activates the RhoA/ROCK pathway, induces F-actin reorganization, improves the migration of ASMCs, and provides a better rationale for targeting the RhoA/ROCK pathway for therapeutic approaches in airway remodeling.
Barriers and enablers to achieving clinical procedure competency-based outcomes in a national paediatric training/residency program—a multi-centered qualitative study
Authors: Khan Waqas Ullah , Twomey John , Ryan Ethel , Martin Therese , Kamal Myeda , Lok Boris Cheng Pak , O’Gorman Clodagh , Byrne Dara 
Published: December 2023

Abstract
Background
In 2018, the Royal College of Physicians of Ireland revised its paediatric training program to a competency-based medical education (CBME) training/residency curriculum. This included a requirement to achieve competence in a number of core procedural skills to progress within the program. Internationally, simulation-based medical education (SBME) is gaining interest as an effective teaching pedagogy for training procedural skill competency. The objectives of this study were to (1) identify enablers and barriers for paediatric trainees to achieve their required procedural competencies, (2) gain insight on the feasibility of achieving the required procedural skills, and (3) explore what simulation-based resources are used as well as their role in achieving the required procedural skill competencies.

Methods
A multi-centered qualitative study using semi-structured interviews was performed. Twenty-four paediatric consultants and trainees were recruited from two academic tertiary hospitals using purposive and snowball sampling. Interviews were conducted between March and September 2021, audio recorded, transcribed, and analyzed using thematic analysis.

Results
Three main themes regarding enablers for achieving procedural competencies were reported and include having protected training time, routine assessments, and a standardized curriculum. Barriers to achieving procedural competencies focused mainly on limited clinical exposure. The use of SBME was recommended by all participants (n = 24, 100%) to assist in achieving procedural competencies and most (n = 15, 62.5%) reported it is feasible to attain the required procedural skills in the paediatric CBME program.

Conclusion
It is feasible to achieve the required procedural competencies for most paediatric trainees, but this can be improved with protected training time, routine assessments, and a standardized curriculum. Barriers to achieving these skills mainly center on limited clinical exposure, which can be remedied by SBME. Further research is warranted to determine the costs and types of SBME tools available as well as teaching pedagogies to support paediatric trainees achieve their required procedural competencies.
USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity
Authors: Kwon Juntae , Zhang Jinmin , Mok Boram , Allsup Samuel , Kim Chul , Toretsky Jeffrey , Han Cecil 
Published: December 2023

AbstractLung squamous cell carcinoma (LUSC) is associated with high mortality and limited targeted therapies. USP13 is one of the most amplified genes in LUSC, yet its role in lung cancer is largely unknown. Here, we established a novel mouse model of LUSC by overexpressing USP13 on KrasG12D/+; Trp53flox/flox background (KPU). KPU-driven lung squamous tumors faithfully recapitulate key pathohistological, molecular features, and cellular pathways of human LUSC. We found that USP13 altered lineage-determining factors such as NKX2-1 and SOX2 in club cells of the airway and reinforced the fate of club cells to squamous carcinoma development. We showed a strong molecular association between USP13 and c-MYC, leading to the upregulation of squamous programs in murine and human lung cancer cells. Collectively, our data demonstrate that USP13 is a molecular driver of lineage plasticity in club cells and provide mechanistic insight that may have potential implications for the treatment of LUSC.
Graphical Abstract
Evidence of brain target engagement in Parkinson’s disease and multiple sclerosis by the investigational nanomedicine, CNM-Au8, in the REPAIR phase 2 clinical trials
Authors: Ren Jimin , Dewey Richard B. , Rynders Austin , Evan Jacob , Evan Jeremy , Ligozio Shelia , Ho Karen S. , Sguigna Peter V. , Glanzman Robert , Hotchkin Michael T. , Dewey Richard B. , Greenberg Benjamin M. 
Published: December 2023

Abstract
Background
Impaired brain energy metabolism has been observed in many neurodegenerative diseases, including Parkinson’s disease (PD) and multiple sclerosis (MS). In both diseases, mitochondrial dysfunction and energetic impairment can lead to neuronal dysfunction and death. CNM-Au8® is a suspension of faceted, clean-surfaced gold nanocrystals that catalytically improves energetic metabolism in CNS cells, supporting neuroprotection and remyelination as demonstrated in multiple independent preclinical models. The objective of the Phase 2 REPAIR-MS and REPAIR-PD clinical trials was to investigate the effects of CNM-Au8, administered orally once daily for twelve or more weeks, on brain phosphorous-containing energy metabolite levels in participants with diagnoses of relapsing MS or idiopathic PD, respectively.

Results
Brain metabolites were measured using 7-Tesla 31P-MRS in two disease cohorts, 11 participants with stable relapsing MS and 13 participants with PD (n = 24 evaluable post-baseline scans). Compared to pre-treatment baseline, the mean NAD+/NADH ratio in the brain, a measure of energetic capacity, was significantly increased by 10.4% after 12 + weeks of treatment with CNM-Au8 (0.584 units, SD: 1.3; p = 0.037, paired t-test) in prespecified analyses of the combined treatment cohorts. Each disease cohort concordantly demonstrated increases in the NAD+/NADH ratio but did not reach significance individually (p = 0.11 and p = 0.14, PD and MS cohorts, respectively). Significant treatment effects were also observed for secondary and exploratory imaging outcomes, including β-ATP and phosphorylation potential across both cohorts.

Conclusions
Our results demonstrate brain target engagement of CNM-Au8 as a direct modulator of brain energy metabolism, and support the further investigation of CNM-Au8 as a potential disease modifying drug for PD and MS.
Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain
Authors: Ko Hyoung-Gon , Chun Heejung , Han Seunghyo , Kaang Bong-Kiun 
Published: December 2023

AbstractPathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through cell adhesion molecules (CAMs) but also regulates the efficiency of chemical signaling. Accumulating evidence has revealed that spinal astrocytes are involved in pathological pain by modulating the efficacy of neurotransmitters such as glutamate and GABA through transporters located in the PAP and by directly regulating synaptic transmission through various gliotransmitters. Although various CAMs contribute to pathological pain, insufficient evidence is available as to whether astrocytic CAMs also have this role. Therefore, more in-depth research is needed on how pathological pain is induced and maintained by astrocytes, especially in the PAP surrounding the synapse, and this will subsequently increase our understanding and treatment of pathological pain.
Histone demethylase KDM4B accelerates the progression of glioblastoma via the epigenetic regulation of MYC stability
Authors: Wang Zhongze , Cai Huarui , Li Zekun , Sun Wei , Zhao Erhu , Cui Hongjuan 
Published: December 2023

Abstract
Background
Glioblastoma (GBM) is the most malignant and invasive human brain tumor. Histone demethylase 4B (KDM4B) is abnormally expressed in GBM, but the molecular mechanisms by which KDM4B affects the malignant tumor progression are not well defined.

Methods
GBM cell lines and xenograft tumor samples were subjected to quantitative PCR (qPCR), Western blot, immunohistochemical staining (IHC), as well as ubiquitination, immunoprecipitation (IP), and chromatin immunoprecipitation (ChIP) assays to investigate the role of KDM4B in the progression of GBM.

Results
Here, we report that KDM4B is an epigenetic activator of GBM progression. Abnormal expression of KDM4B is correlated with a poor prognosis in GBM patients. In GBM cell lines, KDM4B silencing significantly inhibited cell survival, proliferation, migration, and invasion, indicating that KDM4B is essential for the anchorage-independent growth and tumorigenic activity of GBM cells. Mechanistically, KDM4B silencing led to downregulation of the oncoprotein MYC and suppressed the expression of cell cycle proteins and epithelial-to-mesenchymal transition (EMT)-related proteins. Furthermore, we found that KDM4B regulates MYC stability through the E3 ligase complex SCFFBXL3+CRY2 and epigenetically activates the transcription of CCNB1 by removing the repressive chromatin mark histone H3 lysine 9 trimethylation (H3K9me3). Finally, we provide evidence that KDM4B epigenetically activates the transcription of miR-181d-5p, which enhances MYC stability.

Conclusions
Our study has uncovered a KDM4B-dependent epigenetic mechanism in the control of tumor progression, providing a rationale for utilizing KDM4B as a promising therapeutic target for the treatment of MYC-amplified GBM.
Generation of a bank of clinical-grade, HLA-homozygous iPSC lines with high coverage of the Spanish population
Authors: Kuebler B. , Alvarez-Palomo B. , Aran B. , Castaño J. , Rodriguez L. , Raya A. , Querol Giner S. , Veiga A. 
Published: December 2023

Abstract
Background
Induced pluripotent stem cell (iPSC)-derived cell therapies are an interesting new area in the field of regenerative medicine. One of the approaches to decrease the costs of iPSC-derived therapies is the use of allogenic homozygous human leukocyte antigen (HLA)-matched donors to generate iPSC lines and to build a clinical-grade iPSC bank covering a high percentage of the Spanish population.

Methods
The Spanish Stem Cell Transplantation Registry was screened for cord blood units (CBUs) homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes. Seven donors were selected with haplotypes covering 21.37% of the haplotypes of the Spanish population. CD34-positive hematopoietic progenitors were isolated from the mononuclear cell fraction of frozen cord blood units from each donor by density gradient centrifugation and further by immune magnetic labeling and separation using purification columns. Purified CD34 + cells were reprogrammed to iPSCs by transduction with the CTS CytoTune-iPS 2.1 Sendai Reprogramming Kit.

Results
The iPSCs generated from the 7 donors were expanded, characterized, banked and registered. Master cell banks (MCBs) and working cell banks (WCBs) from the iPSCs of each donor were produced under GMP conditions in qualified clean rooms.

Conclusions
Here, we present the first clinical-grade, iPSC haplobank in Spain made from CD34 + cells from seven cord blood units homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes within the Spanish population. We describe their generation by transduction with Sendai viral vectors and their GMP-compliant expansion and banking. These haplolines will constitute starting materials for advanced therapy medicinal product development (ATMP).
AI-driven molecular generation of not-patented pharmaceutical compounds using world open patent data
Authors: Shimizu Yugo , Ohta Masateru , Ishida Shoichi , Terayama Kei , Osawa Masanori , Honma Teruki , Ikeda Kazuyoshi 
Published: December 2023

AbstractDeveloping compounds with novel structures is important for the production of new drugs. From an intellectual perspective, confirming the patent status of newly developed compounds is essential, particularly for pharmaceutical companies. The generation of a large number of compounds has been made possible because of the recent advances in artificial intelligence (AI). However, confirming the patent status of these generated molecules has been a challenge because there are no free and easy-to-use tools that can be used to determine the novelty of the generated compounds in terms of patents in a timely manner; additionally, there are no appropriate reference databases for pharmaceutical patents in the world. In this study, two public databases, SureChEMBL and Google Patents Public Datasets, were used to create a reference database of drug-related patented compounds using international patent classification. An exact structure search system was constructed using InChIKey and a relational database system to rapidly search for compounds in the reference database. Because drug-related patented compounds are a good source for generative AI to learn useful chemical structures, they were used as the training data. Furthermore, molecule generation was successfully directed by increasing and decreasing the number of generated patented compounds through incorporation of patent status (i.e., patented or not) into learning. The use of patent status enabled generation of novel molecules with high drug-likeness. The generation using generative AI with patent information would help efficiently propose novel compounds in terms of pharmaceutical patents. Scientific contribution: In this study, a new molecule-generation method that takes into account the patent status of molecules, which has rarely been considered but is an important feature in drug discovery, was developed. The method enables the generation of novel molecules based on pharmaceutical patents with high drug-likeness and will help in the efficient development of effective drug compounds.
RETRACTED ARTICLE: Node fault diagnosis algorithm for wireless sensor networks based on BN and WSN
Authors: Li Ming 
Published: December 2023

AbstractWireless sensor networks, as an emerging information exchange technology, have been widely applied in many fields. However, nodes tend to become damaged in harsh and complex environmental conditions. In order to effectively diagnose node faults, a Bayesian model-based node fault diagnosis model was proposed. Firstly, a comprehensive analysis was conducted into the operative principles of wireless sensor systems, whereby fault-related features were then extrapolated. A Bayesian diagnostic model was constructed using the maximum likelihood method with sufficient sample features, and a joint tree model was introduced for node diagnosis. Due to the insufficient accuracy of Bayesian models in processing small sample data, a constrained maximum entropy method was proposed as the prediction module of the model. The use of small sample data to obtain the initial model parameters leads to improved performance and accuracy of the model. During parameter learning tests, the limited maximum entropy model outperformed the other two learning models on a smaller dataset of 35 with a distance value of 2.65. In node fault diagnosis, the diagnostic time of the three models was compared, and the average diagnostic time of the proposed diagnostic model was 41.2 seconds. In the node diagnosis accuracy test, the proposed model has the highest node fault diagnosis accuracy, with an average diagnosis accuracy of 0.946, which is superior to the other two models. In summary, the node fault diagnosis model based on Bayesian model proposed in this study has important research significance and practical application value in wireless sensor networks. By improving the reliability and maintenance efficiency of the network, this model provides strong support for the development and application of wireless sensor networks.
Dietary patterns and metabolic dysfunction-associated fatty liver disease in China’s multi-ethnic regions
Authors: Zhu Xingren , Qucuo Nima , Zhang Ning , Tang Dan , Hu Yifan , Xie Xiaofen , Zhao Xing , Meng Qiong , Chen Liling , Jiang Xiaoman , Zhuoma Duoji , Zeng Qibing , Xiao Xiong 
Published: December 2023

Abstract
Background
The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has been rising rapidly in western China. Diet acts as an effective therapy for MAFLD. However, there has been scarce research on the association between a posteriori diet patterns (DPs) and MAFLD in this region.

Method
We identified three a posteriori DPs which were “Sichuan Basin pattern” characterized by a high intake of fish/seafood, poultry, fresh fruit and vegetables, indicating a balanced and modern DP; the “Yunnan–Guizhou Plateau dietary pattern” characterized mainly by a high intake of animal oil and salt, indicating an agricultural and poor DP; and the “Qinghai–Tibet Plateau dietary pattern” characterized by a high intake of coarse grains, wheat products, tubers and tea, respectively, indicating a high-altitude DP. Then, we performed marginal structural models that combined logistic regression and inverse probability exposure weighting (IPEW) to examine the associations between MAFLD and these a posteriori DPs.

Result
We found the “Yunnan–Guizhou Plateau dietary pattern” revealed stronger positive association (OR = 1.50, 95% CI 1.40–1.60) with MAFLD than that of the “Qinghai–Tibet Plateau dietary pattern” (OR = 1.21, 95% CI 1.14–1.30). In contrast, the “Sichuan Basin dietary pattern” showed no significant association with MAFLD. In the further stratified analysis, we found those above associations were stronger in ethnic minorities and rural residents than their counterparts.

Conclusion
Our study implied the unfavourable effects of “Yunnan–Guizhou Plateau dietary pattern” on MAFLD and provided evidence that reducing the intake of oil and sodium may be optimal for MAFLD control in the multi-ethnic region in western China.
Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study
Authors: Risch Nathan , Dubois Jonathan , Etain Bruno , Aouizerate Bruno , Bellivier Frank , Belzeaux Raoul , Dubertret Caroline , Haffen Emmanuel , Januel Dominique , Leboyer Marion , Lefrere Antoine , Samalin Ludovic , Polosan Mircea , Rey Romain , Roux Paul , Schwan Raymund , Walter Michel ,   FondaMental Advanced Centres of Expertise in Bipolar Disorders (FACE-BD) Collaborators, Courtet Philippe , Olié Emilie 
Published: December 2023

Abstract

Background
Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain.

Methods
This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium.

Results
Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35–0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24–0.79; p = 0.008).

Conclusions
This is the first naturalistic study to show lithium’s promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.