bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP51 promotes non-small cell lung carcinoma cell stemness by deubiquitinating TWIST1
Authors: Chen Jin , Wu Zhongqiu , Deng Wenyi , Tang Minying , Wu Lvying , Lin Na , Chen Liuyan , Fu Yunfeng , Zhao Min , Chen Changguo , Li Wenting 
Published: July 2023

Abstract
Background
USP51 is a deubiquitinase (DUB), that is involved in diverse cellular processes. Accumulating evidence has demonstrated that USP51 contributes to cancer development. However, its impact on non-small cell lung carcinoma (NSCLC) cell malignancy is largely unknown.

Methods
In this study, we performed bioinformatics analysis on a dataset from The Cancer Genome Atlas to determine the association between USP51 and cell stemness marker expression in NSCLC patients. RT‒qPCR, Western blotting, and flow cytometry were performed to examine the effects of USP51 depletion on stemness marker expression. Colony formation and tumor sphere formation assays were used to assess the stemness of NSCLC cells. A cycloheximide chase time-course assay and a polyubiquitination assay were carried out to analyze the effects of USP51 on the TWIST1 protein level. TWIST1 was overexpressed in USP51 knockdown NSCLC cells to determine whether TWIST1 is required. The effect of USP51 on the in vivo growth of NSCLC cells was tested through subcutaneous injections in mice.

Results
We found that USP51 deubiquitinates TWIST1, which is significantly upregulated in the tissues of patients with NSCLC and is closely associated with poor prognosis. USP51 expression was positively correlated with the expression of stemness marker CD44, SOX2, NANOG, and OCT4 in NSCLC patients. USP51 depletion attenuated mRNA, protein, and cell surface expression of stemness markers and the stemness of NSCLC cells. Ectopic USP51 expression potentiated the stability of the TWIST1 protein by attenuating its polyubiquitination. In addition, TWIST1 re-expression in NSCLC cells reversed the inhibitory effect of USP51 knockdown on cell stemness. Furthermore, the in vivo results confirmed the suppressive effect of USP51 depletion on NSCLC cell growth.

Conclusions
Our results show that USP51 maintains the stemness of NSCLC cells by deubiquitinating TWIST1. Knocking it down reduces both cell stemness and growth of NSCLC cells.
Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy
Authors: Liu Chong , Zhao Xue-Min , Wang Qiao , Du Ting-Ting , Zhang Mo-Xuan , Wang Hui-Zhi , Li Ren-Peng , Liang Kun , Gao Yuan , Zhou Si-Yu , Xue Tao , Zhang Jian-Guo , Han Chun-Lei , Shi Lin , Zhang Liang-Wen , Meng Fan-Gang 
Published: July 2023

AbstractImpaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.
Effectiveness and therapeutic compliance of digital therapy in shoulder rehabilitation: a randomized controlled trial
Authors: Rizzato Alex , Pizzichemi Martina , Gobbi Erica , Gerardi Adriana , Fortin Claudia , Copcia Ancuta , Paoli Antonio , Marcolin Giuseppe 
Published: July 2023

Abstract
Background
Interactive videogames, virtual reality, and robotics represent a new opportunity for multimodal treatments in many rehabilitation contexts. However, several commercial videogames are designed for leisure and are not oriented toward definite rehabilitation goals. Among the many, Playball® (Playwork, Alon 10, Ness Ziona, Israel) is a therapeutic ball that measures both movement and pressure applied on it while performing rehabilitation games. This study aimed: (i) to evaluate whether the use of this novel digital therapy gaming system was clinically effective during shoulder rehabilitation; (ii) to understand whether this gaming rehabilitation program was effective in improving patients’ engagement (perceived enjoyment and self-efficacy during therapy; attitude and intention to train at home) in comparison to a control non-gaming rehabilitation program.

Methods
A randomized controlled experimental design was outlined. Twenty-two adults with shoulder pathologies were recruited for a rehabilitation program of ten consecutive sessions. A control (CTRL; N = 11; age: 62.0 ± 10.9 yrs) and an intervention group (PG; N = 11; age: 59.9 ± 10.2 yrs) followed a non-digital and a digital therapy, respectively. The day before (T0) and after (T1) the rehabilitation program, pain, strength, and mobility assessments were performed, together with six questionnaires: PENN shoulder Score, PACES-short, Self-efficacy, Attitudes to train at home, Intention to train at home, and System usability scale (SUS).

Results
MANOVA analysis showed significant improvements in pain (p < 0.01), strength (p < 0.05), and PENN Shoulder Score (p < 0.001) in both groups. Similarly, patients’ engagement improved, with significant increments in Self-efficacy (p < 0.05) and attitude (p < 0.05) scores in both groups after the rehabilitation. Pearson correlation showed significant correlations of the Δ scores (T1 - T0) between PACES and Self-efficacy (r = 0.623; p = 0.041) and between PACES and Intention to train at home (r = 0.674; p = 0.023) only in the PG. SUS score after the rehabilitation (74.54 ± 15.60) overcame the cut-off value of 68, representative of good usability of a device.

Conclusions
The investigated digital therapy resulted as effective as an equivalent non-digital therapy in shoulder rehabilitation. The reported positive relationship between the subject’s enjoyment during digital therapy and intention to train at home suggests promising results in possible patient’s exercise engagement at home after the rehabilitation in the medical center.

Retrospectively registered
NCT 05230056.
“My young life, finished already?”: a qualitative study of embedded social stressors and their effects on mental health of low-wage male migrant workers in Singapore
Authors: Farwin Aysha , Low Amanda , Howard Natasha , Yi Huso 
Published: July 2023

Abstract
Background
Increasing evidence shows low-wage migrant workers experience a high prevalence of mental health disorders and adverse health outcomes. Significant disparities in health services usage among migrant workers create added vulnerability to health complications. However, much remains unclear about how vulnerabilities are constructed in migrant worker populations. Additionally, no studies in Singapore have attempted to critically examine the degree to which social environment and structures affect the health and wellbeing of migrant workers. Therefore, this study aimed to critically situate the socio-structural factors creating conditions of vulnerability among migrant workers using a social stress perspective.

Methods
We conducted semi-structured individual and group interviews with migrant workers focused on individual life experiences, community experiences (individual and collective social capital), health (mental and physical health concerns) and stress response behaviours. We used a grounded theory approach to identify sources of stress and stress responses and uncover pathways to social vulnerabilities.

Results
Findings from 21 individual and 2 group interviews revealed that migrant workers were embedded in a cycle of chronic stress driven by structural factors that were mutually reinforced by stressors arising from their social environment. Socio-structural stressors enacted as poor living, working and social conditions resulted in their negative quality-of-life appraisal. Stressors arising from being “foreign” resulted in anticipated stigma, concealment, and healthcare avoidance. These factors synergistically created a persistent mental health burden for migrant workers.

Conclusions
Findings highlight the need to address the mental health burden placed on migrant workers and create avenues for migrant workers to seek psychosocial support to manage their stressors.
Load distribution after unilateral condylar fracture with shortening of the ramus: a finite element model study
Authors: Helmer Loreine M. L. , Klop Cornelis , Lobbezoo Frank , de Lange Jan , Koolstra Jan Harm , Dubois Leander 
Published: July 2023

Abstract
Objectives
After a fracture of the condyle, the fractured ramus is often shortened, which causes premature dental contact on the fractured side and a contralateral open bite. The imbalance could change the load in the temporomandibular joints (TMJs). This change could lead to remodelling of the TMJs to compensate for the imbalance in the masticatory system. The load in the non-fractured condyle is expected to increase, and the load in the fractured condyle to decrease.

Materials and methods
These changes cannot be measured in a clinical situation. Therefore a finite element model (FEM) of the masticatory system was used. In the FEM a fractured right condyle with shortening of the ramus was induced, which varied from 2 to 16 mm.

Results
Results show that, with a larger shortening of the ramus, the load in the fractured condyle decreases and the load in the non-fractured condyle increases. In the fractured condyle during closed mouth a major descent in load, hence a cut-off point, was visible between a shortening of 6 mm and 8 mm.

Conclusions
In conclusion, the change of load could be associated with remodelling on both condyles due to shortening of the ramus.

Clinical relevance
The cut-off point implies that shortening over 6 mm could present more difficulty for the body to compensate.
VA-TIRFM-based SM kymograph analysis for dwell time and colocalization of plasma membrane protein in plant cells
Authors: Su Bodan , Wang Anqi , Xie Daoxin , Shan Xiaoyi 
Published: July 2023

Abstract
Background
The plasma membrane (PM) proteins function in a highly dynamic state, including protein trafficking and protein homeostasis, to regulate various biological processes. The dwell time and colocalization of PM proteins are considered to be two important dynamic features determining endocytosis and protein interactions, respectively. Dwell-time and colocalization detected using traditional fluorescence microscope techniques are often misestimated due to bulk measurement. In particular, analyzing these two features of PM proteins at the single-molecule level with spatiotemporal continuity in plant cells remains greatly challenging.

Results
We developed a single molecular (SM) kymograph method, which is based on variable angle-total internal reflection fluorescence microscopy (VA-TIRFM) observation and single-particle (co-)tracking (SPT) analysis, to accurately analyze the dwell time and colocalization of PM proteins in a spatial and temporal manner. Furthermore, we selected two PM proteins with distinct dynamic behaviors, including AtRGS1 (Arabidopsis regulator of G protein signaling 1) and AtREM1.3 (Arabidopsis remorin 1.3), to analyze their dwell time and colocalization upon jasmonate (JA) treatment by SM kymography. First, we established new 3D (2D+t) images to view all trajectories of the interest protein by rotating these images, and then we chose the appropriate point without changing the trajectory for further analysis. Upon JA treatment, the path lines of AtRGS1-YFP appeared curved and short, while the horizontal lines of mCherry-AtREM1.3 demonstrated limited changes, indicating that JA might initiate the endocytosis of AtRGS1. Analysis of transgenic seedlings coexpressing AtRGS1-YFP/mCherry-AtREM1.3 revealed that JA induces a change in the trajectory of AtRGS1-YFP, which then merges into the kymography line of mCherry-AtREM1.3, implying that JA increases the colocalization degree between AtRGS1 and AtREM1.3 on the PM. These results illustrate that different types of PM proteins exhibit specific dynamic features in line with their corresponding functions.

Conclusions
The SM-kymograph method provides new insight into quantitively analyzing the dwell time and correlation degree of PM proteins at the single-molecule level in living plant cells.
Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC
Authors: Guan Jiezhong , Xu Xi , Qiu Guo , He Chong , Lu Xiaoyue , Wang Kang , Liu Xinyu , Li Yuanyuan , Ling Zihang , Tang Xuan , Liang Yujie , Tao Xiaoan , Cheng Bin , Yang Bo 
Published: July 2023

AbstractBackgroundA growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations.MethodsA cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model.ResultsIncorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identifiedPYGLas a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC.ConclusionPYGLwas identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.
Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials
Authors: Wu Jheng-Yan , Tsai Ya-Wen , Hsu Wan-Hsuan , Liu Ting-Hui , Huang Po-Yu , Chuang Min-Hsiang , Liu Mei-Yuan , Lai Chih-Cheng 
Published: July 2023

Abstract
Background
This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP).

Methods
A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality.

Results
A total of seven RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio [RR], 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I2 = 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD − 0.8; 95% CI − 1.4 to − 0.1; p = 0.02), and hospital stay (MD − 1.1; 95% CI − 2.0 to − 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53).

Conclusions
In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.
The effect of a parental preparation video (Take5) on child and parent anxiety during anaesthetic induction: a protocol for a randomised controlled trial
Authors: Vongkiatkajorn Krittika , Brown Erin A. , Donaldson Alexandra , Rich Vanessa , Paterson Rebecca , Kenardy Justin , Graydon Cameron , Lee-Archer Paul 
Published: July 2023

Abstract
Background
Children undergoing anaesthetic induction experience peri-operative anxiety associated with negative outcomes including emergence delirium, short- and long-term maladaptive behaviour and increased postoperative analgesic requirements. This stems from children’s limited ability to communicate, cope, and regulate intense emotions, leading to high dependency on parental emotional regulation. Previous interventions including video modelling, education and distraction techniques before and during anaesthetic induction have demonstrated significant reduction of anxiety levels. No existing interventions combines evidenced-based psychoeducation video with distraction techniques to support parents to moderate peri-operative anxiety. This study aims to test the efficacy of the Take5 video (now referred to as ‘Take5’), a short and cost-efficient intervention for child peri-operative anxiety.

Methods
A randomised, controlled, superiority trial of Take5 compared to standard care. Take5 was developed by paediatric anaesthetists, child psychologists and a consumer panel of parents of children who had experienced surgery and anaesthesia.
Children aged 3–10 years presenting for elective surgery at a quaternary paediatric facility will be randomly allocated to the intervention group or standard care. Intervention group parents will be shown Take5 prior to accompanying their child for anaesthesia induction. Primary outcomes include child and parent anxiety at induction, measured by the Modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF), the Peri-operative Adult–Child Behavior Interaction Scale (PACBIS) and the Induction Compliance Checklist (ICC). Secondary outcomes include post-operative pain, emergence delirium, parental satisfaction, cost-effectiveness, parent and child psychological well-being at 3 months post procedure and video intervention acceptability.

Discussion
Perioperative anxiety is associated with negative outcome in children including higher pharmacological intervention, delayed procedures, and poor post-recovery outcomes resulting in financial burden on health systems. Current strategies minimising paediatric procedural distress are resource-intensive and have been inconsistent in reducing anxiety and negative postoperative outcomes. The Take5 video is an evidence-driven resource that is designed to prepare and empower parents. The success of Take5 will be evaluated by measuring differences in patient (acute and 3-month), family (satisfaction, acceptability), clinician (feasibility) and health service (cost) outcomes, with each anticipated to benefit children.

Trial registration
Australian and New Zealand Clinical Trial Registry (ACTRN12621001337864) and Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/21/QCHQ/73894).
Exploring the perioperative infection control practices & incidence of surgical site infections in rural India
Authors: Nayan Anveshi , Sarang Bhakti , Khajanchi Monty , Roy Nobhojit , Jesudian Gnanaraj , Menon Nandakumar , Patil Mulki , Kataria Raman , Manoharan Ravikumar , Tongaonkar Rajesh , Dev Ya , Gadgil Anita 
Published: July 2023

Abstract
Background
Surgical site infections (SSIs) affect around a third of patients undergoing surgeries worldwide, annually. It is heterogeneously distributed with a higher burden in low and middle-income countries. Although rural and semi-urban hospitals cater to 60–70% of the Indian population, scarce data regarding SSI rates are available from such hospitals. The study aimed to determine the prevalent SSI prevention practices and existing SSI rates in the smaller rural and semi-urban hospitals in India.

Methods
This is a prospective study performed in two phases involving surgeons and their hospitals from Indian rural and semi-urban regions. In the first phase, a questionnaire was administered to surgeons enquiring into the perioperative SSI prevention practices and five interested hospitals were recruited for phase two which documented the rate of SSIs and factors affecting them.

Results
There was full compliance towards appropriate perioperative sterilisation practices and postoperative mop count practice at the represented hospitals. But prophylactic antimicrobials were continued in the postoperative period in more than 80% of the hospitals. The second phase of our study documented an overall SSI rate of 7.0%. The SSI rates were influenced by the surgical wound class with dirty wounds recording six times higher rate of infection than clean cases.

Conclusions
SSI prevention practices and protocols were in place in all the less-resourced hospitals surveyed. The SSI rates are comparable or lower than other LMIC settings. However, this is accompanied by poor implementation of the antimicrobial stewardship guidelines.