bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and enablers to managing challenging behaviours after traumatic brain injury in the acute hospital setting: a qualitative study
Authors: Block Heather , Bellon Michelle , Hunter Sarah C. , George Stacey 
Published: November 2023

Abstract
Background
Challenging behaviours after traumatic brain injury (TBI) in the acute setting are associated with risk of harm to the patient and staff, delays in commencing rehabilitation and increased length of hospital stay. Few guidelines exist to inform practice in acute settings, and specialist services providing multi-disciplinary expertise for TBI behaviour management are predominantly based in subacute inpatient services. This study aims to investigate acute and subacute staff perspectives of barriers and enablers to effectively managing challenging behaviours after TBI in acute hospital settings.

Methods
Qualitative focus groups were conducted with 28 staff (17 from acute setting, 11 from subacute setting) across two sites who had experience working with patients with TBI. Data were analysed using inductive-deductive reflexive thematic analysis. Data were applied to the constructs of the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to generate themes representing barriers and enablers to managing challenging behaviours after TBI in the acute hospital setting.

Results
Four barriers and three enablers were identified. Barriers include (1) Difficulties with clinical decision making; (2) Concerns for risks to staff and patients; (3) Hospital environment; (4) Intensive resources are required. Enablers were (1) Experienced staff with practical skills; (2) Incorporating person-centred care; and (3) Supportive teams.

Conclusion
These findings can inform pre-implementation planning for future improvements to TBI behaviour management in acute hospital settings. Difficulties with clinical decision making, concerns for risks of injury, the hospital environment and lack of resources are major challenges. Implementation strategies developed to address barriers will need to be trialled, with multi-disciplinary team approaches, and tailored to the acute setting.
A novel autoantibody signatures for enhanced clinical diagnosis of pancreatic ductal adenocarcinoma
Authors: Li Tiandong , Xia Junfen , Yun Huan , Sun Guiying , Shen Yajing , Wang Peng , Shi Jianxiang , Wang Keyan , Yang Hongwei , Ye Hua 
Published: November 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 − 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis.

Methods
A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model.

Results
In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%.

Conclusion
The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.
Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients
Authors: Liu Jiang , Liu Degan , Hu Guangyin , Wang Jingjing , Chen Dadong , Song Chuanjun , Cai Yin , Zhai Chentong , Xu Wenjing 
Published: November 2023

Abstract
Background
Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8+ T cells and CD8+T/CD4+T cell ratio in advanced gastric cancer patients receiving immunotherapy.

Methods
A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People’s Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan–Meier methods and Cox proportional hazards regression models.

Results
The optimal cutoff values for percentages of CD8+ T cells, naive CD8+ T cells (CD8+ Tn) and memory CD8+ T cells (CD8+ Tm) expressing programmed cell death -1(PD-1) as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy.

Conclusion
The circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence.
Outsmarting trogocytosis to boost CAR NK/T cell therapy
Authors: Ramezani Faezeh , Panahi Meymandi Ahmad Reza , Akbari Behnia , Tamtaji Omid Reza , Mirzaei Hamed , Brown Christine E. , Mirzaei Hamid Reza 
Published: November 2023

AbstractChimeric antigen receptor (CAR) NK and T cell therapy are promising immunotherapeutic approaches for the treatment of cancer. However, the efficacy of CAR NK/T cell therapy is often hindered by various factors, including the phenomenon of trogocytosis, which involves the bidirectional exchange of membrane fragments between cells. In this review, we explore the role of trogocytosis in CAR NK/T cell therapy and highlight potential strategies for its modulation to improve therapeutic efficacy. We provide an in-depth analysis of trogocytosis as it relates to the fate and function of NK and T cells, focusing on its effects on cell activation, cytotoxicity, and antigen presentation. We discuss how trogocytosis can mediate transient antigen loss on cancer cells, thereby negatively affecting the effector function of CAR NK/T cells. Additionally, we address the phenomenon of fratricide and trogocytosis-associated exhaustion, which can limit the persistence and effectiveness of CAR-expressing cells. Furthermore, we explore how trogocytosis can impact CAR NK/T cell functionality, including the acquisition of target molecules and the modulation of signaling pathways. To overcome the negative effects of trogocytosis on cellular immunotherapy, we propose innovative approaches to modulate trogocytosis and augment CAR NK/T cell therapy. These strategies encompass targeting trogocytosis-related molecules, engineering CAR NK/T cells to resist trogocytosis-induced exhaustion and leveraging trogocytosis to enhance the function of CAR-expressing cells. By overcoming the limitations imposed by trogocytosis, it may be possible to unleash the full potential of CAR NK/T therapy against cancer. The knowledge and strategies presented in this review will guide future research and development, leading to improved therapeutic outcomes in the field of immunotherapy.
Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study
Authors: Liu Yiran , Wang Shuzhen , Liu Jun , Su Mingrui , Diao Xiaoli , Liang Xiaolong , Zhang Jianxin , Wang Qiuxi , Zhan Yuxin 
Published: November 2023

Abstract
Background
Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia.

Methods
Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV).

Results
As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms.

Conclusion
Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis.
Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).
PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway
Authors: Wang Shu , Cheng Zhiming , Cui Yan , Xu Shuoyan , Luan Qiu , Jing Shan , Du Bulin , Li Xuena , Li Yaming 
Published: November 2023

Abstract
Background
The protein tyrosine phosphatase H receptor (PTPRH) is known to regulate the occurrence and development of pancreatic and colorectal cancer. However, its association with glycolysis in non-small cell lung cancer (NSCLC) is still unclear. In this study, we aimed to investigate the relationship between PTPRH expression and glucose metabolism and the underlying mechanism of action.

Methods
The expression of PTPRH in NSCLC cells was evaluated by IHC staining, qRT‒PCR and Western blotting. The effect of PTPRH on cell biological behavior was evaluated by colony assays, EdU experiments, Transwell assays, wound healing assays and flow cytometry. Changes in F-18-fluorodeoxyglucose (18F‐FDG) uptake and glucose metabolite levels after altering PTPRH expression were detected via a gamma counter and lactic acid tests. The expression of glycolysis-related proteins in NSCLC cells was detected by Western blotting after altering PTPRH expression.

Results
The results showed that PTPRH was highly expressed in clinical patient tissue samples and closely related to tumor diameter and clinical stage. In addition, PTPRH expression was associated with glycometabolism indexes on 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging, the expression level of Ki67 and the expression levels of glycolysis-related proteins. PTPRH altered cell behavior, inhibited apoptosis, and promoted 18F-FDG uptake, lactate production, and the expression of glycolysis-related proteins. In addition, PTPRH modulated the glycometabolism of NSCLC cells via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, as assessed using LY294002 and 740Y-P (an inhibitor and agonist of PI3K, respectively). The same results were validated in vivo using a xenograft tumor model in nude mice. Protein expression levels of PTPRH, glycolysis-related proteins, p-PI3K/PI3K and p-AKT/AKT were measured by IHC staining using a subcutaneous xenograft model in nude mice.

Conclusions
In summary, we report that PTPRH promotes glycolysis, proliferation, migration, and invasion via the PI3K/AKT/mTOR signaling pathway in NSCLC and ultimately promotes tumor progression, which can be regulated by LY294002 and 740Y-P. These results suggest that PTPRH is a potential therapeutic target for NSCLC.

Graphical Abstract
Effects of overground gait training assisted by a wearable exoskeleton in patients with Parkinson’s disease
Authors: Otlet Virginie , Vandamme Clémence , Warlop Thibault , Crevecoeur Frédéric , Ronsse Renaud 
Published: November 2023

AbstractBackgroundIn the recent past, wearable devices have been used for gait rehabilitation in patients with Parkinson’s disease. The objective of this paper is to analyze the outcome of a wearable hip orthosis whose assistance adapts in real time to the patient’s gait kinematics via adaptive oscillators. In particular, this study focuses on a metric characterizing natural gait variability, i.e., the level of long-range autocorrelations (LRA) in series of stride durations.MethodsEight patients with Parkinson’s disease (Hoehn and Yahr stages 1$$-$$-2.5) performed overground gait training three times per week for four consecutive weeks, assisted by a wearable hip orthosis. Gait was assessed based on performance metrics such as the hip range of motion, speed, stride length and duration, and the level of LRA in inter-stride time series assessed using the Adaptive Fractal Analysis. These metrics were measured before, directly after, and 1 month after training.ResultsAfter training, patients increased their hip range of motion, their gait speed and stride length, and decreased their stride duration. These improvements were maintained 1 month after training. Regarding long-range autocorrelations, the population’s behavior was standardized towards a metric closer to the one of healthy individuals after training, but with no retention after 1 month.ConclusionThis study showed that an overground gait training with adaptive robotic assistance has the potential to improve key gait metrics that are typically affected by Parkinson’s disease and that lead to higher prevalence of fall.Trial registration: ClinicalTrials.gov Identifer NCT04314973. Registered on 11 April 2020.
Case report: Takotsubo syndrome following percutaneous coronary intervention
Authors: Lu Rui , Lu Mingjun , He Shangfei , Lu Jing , Liao Yi , Cui Tongtao , Wang Min 
Published: November 2023

Abstract
Background
Takotsubo syndrome (TTS), which is frequently secondary to severe emotional (fear, anxiety, etc.) or physical stress, is an acute reversible heart failure syndrome characterized by temporary left ventricular regional systolic dysfunction. Nevertheless, TTS after percutaneous coronary intervention (PCI) is rare, and its clinical characteristics are easily confused with complications after PCI.

Case presentation
This article reports a case of TTS induced by psychological and physical pressure after successful PCI in our institution. The patient had symptoms comparable to complications after PCI, including V1-V5 ST segment elevation and T wave changes of electrocardiogram (ECG) and troponin elevation. Coronary angiogram, left ventricle opacification (LVO), and cardiac magnetic resonance (CMR) were performed to exclude postoperative complications. Diagnosis of TTS was eventually achieved.

Conclusion
We cannot dismiss the risk of TTS in patients who have unexplained V1-V5 ST segment elevation and T wave changes of ECG and troponin elevation following successful PCI. Meanwhile, medical personnel should provide mental, cultural, and emotional services to patients in addition to essential diagnostic and treatment technical services during the perioperative period.
An expanded clinical spectrum of hypoinsulinaemic hypoketotic hypoglycaemia
Authors: Welters Alena , Leiter Sarah M , Bachmann Nadine , Bergmann Carsten , Hoermann Henrike , Korsch Eckhard , Meissner Thomas , Payne Felicity , Williams Rachel , Hussain Khalid , Semple Robert K. , Kummer Sebastian 
Published: November 2023

Abstract
Background
Hypoketotic hypoglycaemia with suppressed plasma fatty acids and detectable insulin suggests congenital hyperinsulinism (CHI). Severe hypoketotic hypoglycaemia mimicking hyperinsulinism but without detectable insulin has recently been described in syndromic individuals with mosaic genetic activation of post-receptor insulin signalling. We set out to expand understanding of this entity focusing on metabolic phenotypes.

Methods
Metabolic profiling, candidate gene and exome sequencing were performed in six infants with hypoketotic, hypoinsulinaemic hypoglycaemia, with or without syndromic features. Additional signalling studies were carried out in dermal fibroblasts from two individuals.

Results
Two infants had no syndromic features. One was mistakenly diagnosed with CHI. One had mild features of megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, one had non-specific macrosomia, and two had complex syndromes. All required intensive treatment to maintain euglycaemia, with CHI-directed therapies being ineffective. Pathogenic PIK3CA variants were found in two individuals – de novo germline c.323G>A (p.Arg108His) in one non-syndromic infant and postzygotic mosaic c.2740G>A (p.Gly914Arg) in the infant with MCAP. No causal variants were proven in the other individuals despite extensive investigation, although rare variants in mTORC components were identified in one. No increased PI3K signalling in fibroblasts of two individuals was seen.

Conclusions
We expand the spectrum of PI3K-related hypoinsulinaemic hypoketotic hypoglycaemia. We demonstrate that pathogenic germline variants activating post-insulin-receptor signalling may cause non-syndromic hypoinsulinaemic hypoketotic hypoglycaemia closely resembling CHI. This distinct biochemical footprint should be sought and differentiated from CHI in infantile hypoglycaemia. To facilitate adoption of this differential diagnosis, we propose the term “pseudohyperinsulinism”.
The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial
Authors: Nikrad Negin , Farhangi Mahdieh Abbasalizad , Fard Tabrizi Fatemeh Pourteymour , Vaezi Maryam , Mahmoudpour Ata , Mesgari-Abbasi Mehran 
Published: November 2023

Abstract
Background
Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients.

Methods
In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention.

Results
A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05).

Conclusions
In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.
Establishment of a differential diagnosis method and an online prediction platform for AOSD and sepsis based on gradient boosting decision trees algorithm
Authors: Zhou Dongmei , Xie Jingzhi , Wang Jiarui , Zong Juan , Fang Quanquan , Luo Fei , Zhang Ting , Ma Hua , Cao Lina , Yin Hanqiu , Yin Songlou , Li Shuyan 
Published: November 2023

Abstract
Objective
The differential diagnosis between adult-onset Still’s disease (AOSD) and sepsis has always been a challenge. In this study, a machine learning model for differential diagnosis of AOSD and sepsis was developed and an online platform was developed to facilitate the clinical application of the model.

Methods
All data were collected from 42 AOSD patients and 50 sepsis patients admitted to Affiliated Hospital of Xuzhou Medical University from December 2018 to December 2021. In addition, 5 AOSD patients and 10 sepsis patients diagnosed in our hospital after March 2022 were collected for external validation. All models were built using the scikit-learn library (version 1.0.2) in Python (version 3.9.7), and feature selection was performed using the SHAP (Shapley Additive exPlanation) package developed in Python.

Results
The results showed that the gradient boosting decision tree(GBDT) optimization model based on arthralgia, ferritin × lymphocyte count, white blood cell count, ferritin × platelet count, and α1-acid glycoprotein/creatine kinase could well identify AOSD and sepsis. The training set interaction test (AUC: 0.9916, ACC: 0.9457, Sens: 0.9556, Spec: 0.9578) and the external validation also achieved satisfactory results (AUC: 0.9800, ACC: 0.9333, Sens: 0.8000, Spec: 1.000). We named this discrimination method AIADSS (AI-assisted discrimination of Still’s disease and Sepsis) and created an online service platform for practical operation, the website is http://cppdd.cn/STILL1/.

Conclusion
We created a method for the identification of AOSD and sepsis based on machine learning. This method can provide a reference for clinicians to formulate the next diagnosis and treatment plan.