bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial
Authors: Yu Edward , Allan Alison L. , Sanatani Michael , Lewis Debra , Warner Andrew , Dar A. Rashid , Yaremko Brian P. , Lowes Lori E. , Palma David A. , Raphael Jacques , Vincent Mark D. , Rodrigues George B. , Fortin Dalilah , Inculet Richard I. , Frechette Eric , Bierer Joel , Law Jeffery , Younus Jawaid , Malthaner Richard A. 
Published: July 2022

Abstract
Background
Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy.

Methods
We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis.

Results
CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001).

Conclusion
The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.
Evaluation of the safety of tranexamic acid use in pediatric patients undergoing spinal fusion surgery: a retrospective comparative cohort study
Authors: Ivasyk Iryna , Chatterjee Abhinaba , Jordan Catherine , Geiselmann Matthew T. , Chang Peter S. , Kamel Hooman , Khormaee Sariah 
Published: July 2022

Abstract
Background
Pediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database.

Methods
Retrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period.

Results
In this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA.

Conclusions
The use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery.
Large hiatus hernia: time for a paradigm shift?
Authors: Rajkomar Kheman , Berney Christophe R. 
Published: July 2022

Abstract
Background
Laparoscopic large hiatal hernia (LHH) repair remains a challenge despite three decades of ongoing attempts at improving surgical outcome. Its rarity and complexity, coupled with suboptimal initial approach that is usually best suited for small symptomatic herniae have contributed to unacceptable higher failure rates.

Results
We have therefore undertaken a systematic appraisal of LHH with a view to clear out our misunderstandings of this entity and to address dogmatic practices that may have contributed to poor outcomes.

Conclusions
First, we propose strict criteria to define nomenclature in LHH and discuss ways of subcategorising them. Next, we discuss preoperative workup strategies, paying particular attention to any relevant often atypical symptoms, indications for surgery, timing of surgery, role of surgery in the elderly and emphasizing the key role of a preoperative CT imaging in evaluating the mediastinum. Some key dissection methods are then discussed with respect to approach to the mediastinal sac, techniques to avoid/deal with pleural breach and rationale to avoid Collis gastroplasty. The issues pertaining to the repair phase are also discussed by evaluating the merits of the cruroplasty, fundoplication types and gastropexy. We end up debating the role of mesh reinforcement and assess the evidence with regards to recurrence, reoperation rate, complications, esophageal dilatation, delayed gastric emptying and mortality. Lastly, we propose a rationale for routine postoperative investigations.
Effect of Enterococcus faecalis OG1RF on human calvarial osteoblast apoptosis
Authors: Li Yang , Sun Shuyu , Wen Cheng , Zhong Jialin , Jiang Qianzhou 
Published: July 2022

Abstract
Background
Enterococcus faecalis is a dominant pathogen in the root canals of teeth with persistent apical periodontitis (PAP), and osteoblast apoptosis contributes to imbalanced bone remodelling in PAP. Here, we investigated the effect of E. faecalis OG1RF on apoptosis in primary human calvarial osteoblasts. Specifically, the expression of apoptosis-related genes and the role of anti-apoptotic and pro-apoptotic members of the BCL-2 family were examined.

Methods
Primary human calvarial osteoblasts were incubated with E. faecalis OG1RF at multiplicities of infection corresponding to infection time points. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, caspase-3/-8/-9 activity assay, polymerase chain reaction (PCR) array, and quantitative real-time PCR were used to assess osteoblast apoptosis.

Results
E. faecalis infection increased the number of early- and late-phase apoptotic cells and TUNEL-positive cells, decreased the mitochondrial membrane potential (ΔΨm), and activated the caspase-3/-8/-9 pathway. Moreover, of all 84 apoptosis-related genes in the PCR array, the expression of 16 genes was upregulated and that of four genes was downregulated in the infected osteoblasts. Notably, the mRNA expression of anti-apoptotic BCL2 was downregulated, whereas that of the pro-apoptotic BCL2L11, HRK, BIK, BMF, NOXA, and BECN1 and anti-apoptotic BCL2A1 was upregulated.

Conclusions
E. faecalis OG1RF infection triggered apoptosis in human calvarial osteoblasts, and BCL-2 family members acted as regulators of osteoblast apoptosis. Therefore, BCL-2 family members may act as potential therapeutic targets for persistent apical periodontitis.
Early experiences with quality-assured HbA1c and professional glucose point-of-care testing in general practice: a cross-sectional observational study among patients, nurses and doctors
Authors: Smits Marleen , Hopstaken Rogier , Terhaag Lusan , de Kort Gijs , Giesen Paul 
Published: July 2022

Abstract
Background
Point-of-care testing (POCT) is increasingly used in primary care. The rapid availability of the test result during the patient encounter increases the potential for patients and care providers to make a direct and joint decision on disease management. Our aim was to get insight into the first experiences of patients and healthcare professionals after introducing quality-controlled HbA1c and professional glucose POCT in diabetes care in their own general practices.

Methods
A cross-sectional observational study using paper questionnaires for patients, nurses and general practitioners (GPs) in 13 general practices in the Netherlands. HbA1c and professional glucose POCT was introduced after training and under day-to-day quality control. Patients filled in the questionnaire immediately after the test; nurses and GPs after a minimum period of three months from the starting date. Descriptive data analyses were performed.

Results
A total of 1551 fingerstick blood POC tests were performed (1126 HbA1c; 425 Glucose). For HbA1c POCT, 84 patients, 29 nurses and 11 GPs filled in the questionnaires. For professional glucose POCT, 30 patients, 17 nurses and 8 GPs responded. Response rates varied between 24 and 56%. Patients, nurses and GPs were generally (very) satisfied with the novel POC tests. Patients were most positive about the location (in the GPs’ office) and execution of the POC test (by their own nurse), and the speed of the test result. Almost all nurses indicated to have sufficient knowledge and skills to perform the test. Both nurses and GPs had confidence in the test results and indicated they experienced a higher patient satisfaction than with regular blood tests. Perceived disadvantages were the time required to regularly calibrate the devices and the extension of the consultation time because of the test. Patients, nurses and GPs generally expressed they wanted to continue performing these POC tests in routine diabetes care.

Conclusions
Patients, nurses and GPs expressed (very) positive first experiences after introducing HbA1c and professional glucose testing on two high-quality POCT devices in their own general practices. Further research, with a random selection procedure of practices and patients and in other regions and countries, is recommended to confirm these findings.
Evaluation of COVID-19 ECHO training program for healthcare workers in India - A Mixed-Method Study
Authors: Panda Rajmohan , Mishra Nivedita , Lahoti Supriya , Prabhu Rajath R , Mishra Arti , Singh Kalpana , Rai Kumud 
Published: July 2022

Abstract
Background
The Coronavirus Disease 2019 (COVID-19) has severely challenged healthcare delivery systems worldwide. Healthcare Workers were unable to assess and manage the cases due to limited knowledge of treating the virus and inadequate infrastructure. Digital interventions played a crucial role in the training of healthcare workers to get through the pandemic. Project Extension for Community Healthcare Outcomes (ECHO) initiated the COVID-ECHO telementoring program for strengthening the knowledge and skills of healthcare workers. The study aimed at assessing the effects of the ECHO telementoring model in the capacity building of healthcare workers in the context of COVID-19 in India.

Method
We adopted a mixed-method approach with a parallel combination design. A quantitative survey was used to measure changes in the knowledge and self-efficacy among doctors and nurses. In-depth Interviews were used for qualitative exploration of perceptions and experiences of all the study participants. Student t-test and ANOVA were used to assess significant differences between mean scores across participant characteristics for different themes. Statistical significance was set at p < 0.05. In-depth Interviews were analyzed using Framework Analysis. The evaluation followed the first five levels of Moore’s model.

Results
The results highlighted the strengthening of knowledge and skills of healthcare workers in the assessment and management of COVID-19 after the ECHO training. Learning and performance ratings were high as 96% reported an increase in knowledge and 98% were able to apply it in their clinical practices. The key challenges identified were technical issues like internet connectivity and lack of interaction due to limited visual connection. The hybrid sessions, use of video camera, feedback mechanism, and inclusion of Continuing Medical Education were recommended by participants to improve the model.

Conclusions
The findings of this study are an important addition to the pre-existing literature supporting the replicability of the ECHO model in the upskilling of healthcare professionals working in underserved and remote areas, not only in the context of COVID-19 but also in other public health domains. To enhance the effectiveness of this ECHO model, the study findings may be used to refine the model and improve the areas of concern.
Empowerment training to support service user involvement in mental health system strengthening in rural Ethiopia: a mixed-methods pilot study
Authors: Abayneh Sisay , Lempp Heidi , Rai Sauharda , Girma Eshetu , Getachew Medhanit , Alem Atalay , Kohrt Brandon A. , Hanlon Charlotte 
Published: July 2022

Abstract
Background
Increased service user involvement is recommended to improve weak mental health systems in low-and middle-income countries (LMICs). However, involvement is rarely implemented and interventions to support involvement are sparse. In this study we evaluated the acceptability, feasibility and perceived outcomes of an empowerment and training program for service users and health professionals to facilitate service user involvement in mental health system strengthening in rural Ethiopia.

Methods
REducing Stigma among HealthcAreProvidErs (RESHAPE) is a training curriculum for service users, their caregivers and aspirational health workers, which uses PhotoVoice methodology, to prepare them in participation of mental health systems strengthening in LMICs. We delivered the RESHAPE training augmented with empowerment content developed in Ethiopia. The interactive face-to-face training was delivered to service users and caregivers (over 10 days), and health professionals (1 day) separately. The study was an uncontrolled, convergent mixed-methods design. The quantitative data consisted of process data, satisfaction questionnaire, and a retrospective pre-test survey. Qualitative data included exit and follow-up in-depth interviews with the service users. Descriptive statistics were performed for quantitative data, and qualitative data were thematically analysed. The findings were integrated through triangulation for convergent themes following analysis.

Results
Twelve service users, 12 caregivers and 18 health professionals were enrolled, and completed the training. Participants valued the content and delivery process; the standard of the training program met their expectations and participation led to positive gains in understanding about mental illness, stigma, service-user involvement and human rights. The qualitative findings identified positive impacts, including increased self-confidence, sense of empowerment, social - and perceived therapeutic benefits.

Conclusions
We found that the RESHAPE training with added content for Ethiopia, delivered using the PhotoVoice methodology, is feasible, acceptable and of value to develop and implement training programmes which can empower service users to be involved in mental health system strengthening in this setting. Further study to assess the impact on health systems strengthening is warranted.
Carrying both COL1A2 and FBN2 gene heterozygous mutations results in a severe skeletal clinical phenotype: an affected family
Authors: Chen Jing , Xiang Qinqin , Xiao Xiao , Xu Bocheng , Xie Hanbing , Wang He , Yang Mei , Liu Shanling 
Published: July 2022

Abstract
Background
Osteogenesis imperfecta (OI) is the most common monogenic disease of the skeletal system and is usually caused by mutations in the COL1A1 or COL1A2 genes. Congenital contractural arachnodactyly syndrome (CCA) is an autosomal dominant hereditary disease of connective tissue. To date, the FBN2 gene is the only gene reported to cause CCA. Researchers found that COL1A2 and FBN2 are both involved in the extracellular matrix organization pathway. These findings suggest that these two genes play an important role in a similar mechanism and may trigger a synergistic effect.

Methods
Trio-whole-exome sequencing (Trio-WES) was performed to analyse the underlying genetic cause of a proband with OI in a Chinese family. Sanger sequencing was used to validate the mutations in 3 members of the family with OI with varying degrees of severity of skeletal abnormalities and the members with no clinical signs.

Result
A c.3304G > C mutation in the COL1A2 gene (p.Gly1102Arg) and a novel c.4108G > T mutation in the FBN2 gene (p.Glu1370*) were detected in the proband, an affected member of the family. The affected individuals with both mutations present a more severe phenotype, while affected individuals present a milder phenotype if only the mutation in COL1A2 is detected (c.3304G > C). The unaffected individual in this family did not have any mutations in the COL1A2 gene or FBN2 gene.

Conclusion
Our study is the first clinical report to indicate that patients carrying concomitant mutations in both the COL1A2 and FBN2 genes may present with more severe skeletal abnormalities. Furthermore, our study suggests the possibility of synergistic effects between the COL1A2 and FBN2 genes.
A novel signature derived from metabolism-related genes GPT and SMS to predict prognosis of laryngeal squamous cell carcinoma
Authors: Shen Yujie , Huang Qiang , Zhang Yifan , Hsueh Chi-Yao , Zhou Liang 
Published: July 2022

Abstract
Background
A growing body of evidence has suggested the involvement of metabolism in the occurrence and development of tumors. But the link between metabolism and laryngeal squamous cell carcinoma (LSCC) has rarely been reported. This study seeks to understand and explain the role of metabolic biomarkers in predicting the prognosis of LSCC.

Methods
We identified the differentially expressed metabolism-related genes (MRGs) through RNA-seq data of The Cancer Genome Atlas (TCGA) and Gene set enrichment analysis (GSEA). After the screening of protein–protein interaction (PPI), hub MRGs were analyzed by least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic signature. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) was applied to verify the effectiveness of the prognostic signature in four cohorts (TCGA cohort, GSE27020 cohort, TCGA-sub1 cohort and TCGA-sub2 cohort). The expressions of the hub MRGs in LSCC cell lines and clinical samples were verified by quantitative reverse transcriptase PCR (qRT-PCR). The immunofluorescence staining of the tissue microarray (TMA) was carried out to further verify the reliability and validity of the prognostic signature. Cox regression analysis was then used to screen for independent prognostic factors of LSCC and a nomogram was constructed based on the results.

Results
Among the 180 differentially expressed MRGs, 14 prognostic MRGs were identified. A prognostic signature based on two MRGs (GPT and SMS) was then constructed and verified via internal and external validation cohorts. Compared to the adjacent normal tissues, SMS expression was higher while GPT expression was lower in LSCC tissues, indicating poorer outcomes. The prognostic signature was proven as an independent risk factor for LSCC in both internal and external validation cohorts. A nomogram based on these results was developed for clinical application.

Conclusions
Differentially expressed MRGs were found and proven to be related to the prognosis of LSCC. We constructed a novel prognostic signature based on MRGs in LSCC for the first time and verified it via different cohorts from both databases and clinical samples. A nomogram based on this prognostic signature was developed.
Modelling intra-muscular contraction dynamics using in silico to in vivo domain translation
Authors: Ali Hazrat , Umander Johannes , Rohlén Robin , Röhrle Oliver , Grönlund Christer 
Published: July 2022

Abstract
Background
Advances in sports medicine, rehabilitation applications and diagnostics of neuromuscular disorders are based on the analysis of skeletal muscle contractions. Recently, medical imaging techniques have transformed the study of muscle contractions, by allowing identification of individual motor units’ activity, within the whole studied muscle. However, appropriate image-based simulation models, which would assist the continued development of these new imaging methods are missing. This is mainly due to a lack of models that describe the complex interaction between tissues within a muscle and its surroundings, e.g., muscle fibres, fascia, vasculature, bone, skin, and subcutaneous fat. Herein, we propose a new approach to overcome this limitation.

Methods
In this work, we propose to use deep learning to model the authentic intra-muscular skeletal muscle contraction pattern using domain-to-domain translation between in silico (simulated) and in vivo (experimental) image sequences of skeletal muscle contraction dynamics. For this purpose, the 3D cycle generative adversarial network (cycleGAN) models were evaluated on several hyperparameter settings and modifications. The results show that there were large differences between the spatial features of in silico and in vivo data, and that a model could be trained to generate authentic spatio-temporal features similar to those obtained from in vivo experimental data. In addition, we used difference maps between input and output of the trained model generator to study the translated characteristics of in vivo data.

Results
This work provides a model to generate authentic intra-muscular skeletal muscle contraction dynamics that could be used to gain further and much needed physiological and pathological insights and assess and overcome limitations within the newly developed research field of neuromuscular imaging.