bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice
Authors: Zhu Wei Zhong , Olson Aaron , Portman Michael , Ledee Dolena 
Published: December 2020

AbstractBackgroundSex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice.MethodsAged (18–20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting.ResultsSerial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference andp < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways.ConclusionWe identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction.
Predicting 30-days mortality for MIMIC-III patients with sepsis-3: a machine learning approach using XGboost
Authors: Hou Nianzong , Li Mingzhe , He Lu , Xie Bing , Wang Lin , Zhang Rumin , Yu Yong , Sun Xiaodong , Pan Zhengsheng , Wang Kai 
Published: December 2020

AbstractBackgroundSepsis is a significant cause of mortality in-hospital, especially in ICU patients. Early prediction of sepsis is essential, as prompt and appropriate treatment can improve survival outcomes. Machine learning methods are flexible prediction algorithms with potential advantages over conventional regression and scoring system. The aims of this study were to develop a machine learning approach using XGboost to predict the 30-days mortality for MIMIC-III Patients with sepsis-3 and to determine whether such model performs better than traditional prediction models.MethodsUsing the MIMIC-III v1.4, we identified patients with sepsis-3. The data was split into two groups based on death or survival within 30 days and variables, selected based on clinical significance and availability by stepwise analysis, were displayed and compared between groups. Three predictive models including conventional logistic regression model, SAPS-II score prediction model and XGBoost algorithm model were constructed by R software. Then, the performances of the three models were tested and compared by AUCs of the receiver operating characteristic curves and decision curve analysis. At last, nomogram and clinical impact curve were used to validate the model.ResultsA total of 4559 sepsis-3 patients are included in the study, in which, 889 patients were death and 3670 survival within 30 days, respectively. According to the results of AUCs (0.819 [95% CI 0.800–0.838], 0.797 [95% CI 0.781–0.813] and 0.857 [95% CI 0.839–0.876]) and decision curve analysis for the three models, the XGboost model performs best. The risk nomogram and clinical impact curve verify that the XGboost model possesses significant predictive value.ConclusionsUsing machine learning technique by XGboost, more significant prediction model can be built. This XGboost model may prove clinically useful and assist clinicians in tailoring precise management and therapy for the patients with sepsis-3.
Exploration of predictive and prognostic alternative splicing signatures in lung adenocarcinoma using machine learning methods
Authors: Cai Qidong , He Boxue , Zhang Pengfei , Zhao Zhenyu , Peng Xiong , Zhang Yuqian , Xie Hui , Wang Xiang 
Published: December 2020

Abstract
Background
Alternative splicing (AS) plays critical roles in generating protein diversity and complexity. Dysregulation of AS underlies the initiation and progression of tumors. Machine learning approaches have emerged as efficient tools to identify promising biomarkers. It is meaningful to explore pivotal AS events (ASEs) to deepen understanding and improve prognostic assessments of lung adenocarcinoma (LUAD) via machine learning algorithms.

Method
RNA sequencing data and AS data were extracted from The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database. Using several machine learning methods, we identified 24 pairs of LUAD-related ASEs implicated in splicing switches and a random forest-based classifiers for identifying lymph node metastasis (LNM) consisting of 12 ASEs. Furthermore, we identified key prognosis-related ASEs and established a 16-ASE-based prognostic model to predict overall survival for LUAD patients using Cox regression model, random survival forest analysis, and forward selection model. Bioinformatics analyses were also applied to identify underlying mechanisms and associated upstream splicing factors (SFs).

Results
Each pair of ASEs was spliced from the same parent gene, and exhibited perfect inverse intrapair correlation (correlation coefficient = − 1). The 12-ASE-based classifier showed robust ability to evaluate LNM status of LUAD patients with the area under the receiver operating characteristic (ROC) curve (AUC) more than 0.7 in fivefold cross-validation. The prognostic model performed well at 1, 3, 5, and 10 years in both the training cohort and internal test cohort. Univariate and multivariate Cox regression indicated the prognostic model could be used as an independent prognostic factor for patients with LUAD. Further analysis revealed correlations between the prognostic model and American Joint Committee on Cancer stage, T stage, N stage, and living status. The splicing network constructed of survival-related SFs and ASEs depicts regulatory relationships between them.

Conclusion
In summary, our study provides insight into LUAD researches and managements based on these AS biomarkers.
A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone
Authors: Staedt Henning , Dau Michael , Schiegnitz Eik , Thiem Daniel G. E. , Tagadiuc Olga , Palarie Victor , Ottl Peter , Al-Nawas Bilal , Kämmerer Peer W. 
Published: December 2020

AbstractBackgroundThe aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo.MethodsEight weeks after formation of a lateral full-thickness perforating bone defect in the mandible of 40 rabbits, bovine bone substitute with (“+”;n = 20) and without (“-”;n = 20) collagen membrane was applied. Blood and bone was collected 24, 72 h, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points.ResultsTwenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in “+” group when compared to “-” (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in “+” (allp < 0.05). Fourteen days after surgery, the significant highest values for all bone turnover markers were detected in “-” (allp < 0.05). A significant difference in favor of group “-” could also be detected after 3 weeks in terms of both acid phosphatases (p < 0.05). In histology, no significant differences could be detected.ConclusionBone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.
Factors associated with substance use disorder treatment completion: a cross-sectional analysis of justice-involved adolescents
Authors: Johnson Micah E. , Tran Dieu X. 
Published: December 2020

Abstract
Background
Substance use disorders (SUD) are prevalent among those in the juvenile justice system. SUD treatment programs implemented in correctional settings can prevent overdose and other health-related problems among an underserved health disparity population. However, only a fraction of justice-involved adolescents with SUDs complete a treatment program and the factors associated with treatment completion among adolescents in the criminal justice system have not been thoroughly investigated.

Methods
Using cross-sectional data on 25,587 adolescents from the Florida Department of Juvenile Justice (FLDJJ) who met the criteria for SUD treatment, the study investigated the factors associated with the completion of SUD treatment. Sociodemographic, mental health, and other variables were examined.

Results
Several factors were associated with an increased likelihood of SUD treatment completion: previous participation in treatment programs, prior drug and alcohol education class attendance, and involvement in court-directed programs. Additional factors included multiple incarcerations, and strong financial and support networks.

Conclusions
The strongest factors associated with a higher likelihood of SUD treatment completion among adolescents in the justice system are ones that can be translated into programs and practices. Repeated referrals to treatment, court-directed programs, and strong support networks may yield higher rates of completion.
Supraspinatus tendon transosseous vs anchor repair surgery: a comparative study of mechanical recovery in the rabbit
Authors: Chaler Joaquim , Louati Hakim , Uhthoff Hans K. , Trudel Guy 
Published: December 2020

Abstract
Background
Supraspinatus (SSP) tendon ruptures requiring surgical repair are common. Arthroscopic suture anchor fixation has gradually replaced transosseous repair in supraspinatus tendon tear. Our objective was to compare mechanical properties between transosseous and anchor supraspinatus repair in the first 6 postoperative weeks in a rabbit model.

Methods
One hundred and fifty-two rabbits had one supraspinatus tendon repaired either with an anchor suture 1 week after detachment or with transosseous sutures. Rabbits were euthanized at 0, 1, 2, 4 or 6 postoperative weeks. Experimental and contralateral tendons (304 tendons) were mechanically tested to failure. Data are expressed as percent of contralateral.

Results
Anchor repair had higher loads to failure compared to transosseous repair, at immediate repair (week 0, 52 ± 21% vs 25 ± 17%, respectively; p = 0.004) and at 1 postoperative week (64 ± 32% vs 28 ± 10%; p = 0.003) with no difference after 2 weeks. There was no difference in stiffness. Transosseous repairs showed higher rates of midsubstance failures compared to anchor repairs at 1 (p = 0.004) and 2 postoperative weeks (p < 0.001). Both transosseous and anchor repairs restored supraspinatus mechanical properties after 4 postoperative weeks.

Conclusion
Anchor repair provided better initial tensile strength while transosseous repair led to a faster normalization (namely, midsubstance) of the mode of failure. Research to optimize supraspinatus repair may need to consider the advantages from both surgical approaches.
Electrocution as an alternative euthanasia method to blunt force trauma to the head followed by exsanguination for non-viable piglets
Authors: Husheer Johannes , Luepke Matthias , Dziallas Peter , Waldmann Karl-Heinz , von Altrock Alexandra 
Published: December 2020

Abstract
Background
On farms, the currently approved and most widely practised method of euthanising non-viable piglets is blunt force trauma to the head followed by exsanguination. However, the use of this method is criticised due to public perceptions and aversion to the methodology by caretakers. Therefore, electrocution after electrical stunning was examined as an alternative approach in 80 hybrid piglets. Initially, electrocution was simulated with finite element analysis using a computer piglet-model, where current density in the heart was visualised and size and position of the electrodes were defined. The following step investigated electrical parameters for electrocution in anaesthetised piglets; first, with a constant voltage power source and then with a constant current power source. The electrical stunning was examined using the constant current supply. Finally, the results of electrical stunning and electrocution were verified in 25 healthy piglets with a body weight between 1 and 2 kg. Unconsciousness was proven by testing palpebral, corneal and nociceptive reflexes. Time of death was confirmed by electroencephalography (EEG) and electrocardiography (ECG) records.

Results
Stunning succeeded with the preset of 1.3 A and 50 Hz, placing the electrodes on both sides of the head between the eyes and ears using different timespans between 8 and 20 s. Prolonged electrical flow resulted in reduced paddling movements after the epileptic seizure, and allowed undisturbed reflex tests and installation of electrodes for EEG and ECG recording during electrocution. Using 0.75 A and 400 Hz, pin-shaped electrodes were first positioned on both sides of the chest for 5 s, followed by a break of 20–30 s and a second current flow, whereby the electrodes were placed above the withers and the sternum for 5 s. Cardiac arrest and an isoelectric EEG were induced within 3 min after the onset of the electrical flow through the chest. The most obvious indicator of effective stunning and electrocution was termination of rhythmic breathing. Piglets with cardiac arrest showed only single gasps lasting up to 3 min after electrocution.

Conclusions
The evaluated stunning and electrocution protocol might ease concerns about timely piglet euthanasia. However, this should be verified in non-viable piglets to exclude influencing factors like dehydration and diseases.
The use of pasung for people with mental illness: a systematic review and narrative synthesis
Authors: Hidayat Muhamad Taufik , Lawn Sharon , Muir-Cochrane Eimear , Oster Candice 
Published: December 2020

AbstractBackgroundPasung is the term used in Indonesia and a number of other countries for seclusion and restraint of people with mental illness in the community, usually at home by their family. While pasung has been banned because it is contrary to human rights, its practice continues to exist within the community, particularly where community mental health services are limited, and in the absence of adequate social support, and pervasive negatives beliefs about mental illness. It is essential to understand the reasons for the ongoing use of pasung and to examine potential solutions.MethodsA systematic review and narrative synthesis of peer-reviewed international literature was conducted to identify the socio-cultural contexts for pasung use, and interventions to address it. The analysis draws on the socio-ecological framework, which focused on relationships between the individual and their environment.ResultFifty published articles were included in the review; all studies were conducted in Asia and Africa, with 32 undertaken in Indonesia. Most studies were qualitative (n = 21). Others included one case–control study, one cross-sectional study, and seven surveys; only four studies examined the application of an intervention, and each used a pre and post methodology. Of these, two studies tested psychoeducational interventions which aimed to overcome family burden due to pasung, and each suggested a community mental health approach. The remaining two studies evaluated the intervention of ‘unlocking’; one study used a community-based culturally sensitive approach, and the other used a community-based rehabilitation program. Reasons for pasung given by family appear to be as a last resort and in the absence of other supports to help them care for the person with severe mental illness.ConclusionThe findings highlight that a mixture of individual, interpersonal, community and policy interventions are needed to reduce the use of pasung. While consumer and carer involvement as part of a socio-ecological approach is understood to be effective in reducing pasung, an understanding of how to elaborate this in the management of pasung remains elusive.Review RegistrationCRD42020157543: CRD
Abnormally activated OPN/integrin αVβ3/FAK signalling is responsible for EGFR-TKI resistance in EGFR mutant non-small-cell lung cancer
Authors: Fu Yulong , Zhang Yang , Lei Zhe , Liu Ting , Cai Tingting , Wang Anqi , Du Wenwen , Zeng Yuanyuan , Zhu Jianjie , Liu Zeyi , Huang Jian-an 
Published: December 2020

AbstractBackgroundAcquired epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance limits the long-term clinical efficacy of tyrosine kinase-targeting drugs. Although most of the mechanisms of acquired EGFR-TKI resistance have been revealed, the mechanism of ~ 15% of cases has not yet been elucidated.MethodsCell viability was analysed using the Cell Counting Kit-8 (CCK-8) assay. Proteome profiler array analysis was performed to find proteins contributing to acquired EGFR-TKI resistance. Secreted OPN was detected by ELISA. Immunohistochemical analysis was conducted to detect expression of integrin αV in NSCLC tissue. The effect of VS-6063 on apoptosis and proliferation of PC9 gefitinib-resistant cells was detected by fluorescence-activated cell sorting (FACS) and clonogenic assays. A mouse xenograft model was used to assess the effect of VS-6063 on the sensitivity of PC9 gefitinib-resistant cells to gefitinib.ResultsOPN was overexpressed in acquired EGFR-TKI-resistant NSCLCs. Secreted OPN contributed to acquired EGFR-TKI resistance by activating the integrin αVβ3/FAK pathway. Inhibition of FAK signalling increased sensitivity to EGFR-TKIs in PC9 gefitinib-resistant cells both in vitro and in vivo.ConclusionsOPN contributes to acquired EGFR-TKI resistance by up-regulating expression of integrin αVβ3, which activates the downstream FAK/AKT and ERK signalling pathways to promote cell proliferation in NSCLC.
Proteomic signatures of 16 major types of human cancer reveal universal and cancer-type-specific proteins for the identification of potential therapeutic targets
Authors: Zhou Yangying , Lih T. Mamie , Pan Jianbo , Höti Naseruddin , Dong Mingming , Cao Liwei , Hu Yingwei , Cho Kyung-Cho , Chen Shao-Yung , Eguez Rodrigo Vargas , Gabrielson Edward , Chan Daniel W. , Zhang Hui , Li Qing Kay 
Published: December 2020

Abstract
Background
Proteomic characterization of cancers is essential for a comprehensive understanding of key molecular aberrations. However, proteomic profiling of a large cohort of cancer tissues is often limited by the conventional approaches.

Methods
We present a proteomic landscape of 16 major types of human cancer, based on the analysis of 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent tissues, and 12 normal tissues, using mass spectrometry-based data-independent acquisition approach.

Results
In our study, a total of 8527 proteins were mapped to brain, head and neck, breast, lung (both small cell and non-small cell lung cancers), esophagus, stomach, pancreas, liver, colon, kidney, bladder, prostate, uterus and ovary cancers, including 2458 tissue-enriched proteins. Our DIA-based proteomic approach has characterized major human cancers and identified universally expressed proteins as well as tissue-type-specific and cancer-type-specific proteins. In addition, 1139 therapeutic targetable proteins and 21 cancer/testis (CT) antigens were observed.

Conclusions
Our discoveries not only advance our understanding of human cancers, but also have implications for the design of future large-scale cancer proteomic studies to assist the development of diagnostic and/or therapeutic targets in multiple cancers.
Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study
Authors: Bagate François , Rouzé Anahita , Zerimech Farid , Boissier Florence , Labbe Vincent , Razazi Keyvan , Carteaux Guillaume , de Prost Nicolas , Balduyck Malika , Maboudou Patrice , Nseir Saad , Mekontso Dessap Armand 
Published: December 2020

AbstractBackgroundMicroaspiration of gastric and oropharyngeal secretions is the main causative mechanism of ventilator-associated pneumonia (VAP). Transesophageal echocardiography (TEE) is a routine investigation tool in intensive care unit and could enhance microaspiration. This study aimed at evaluating the impact of TEE on microaspiration and VAP in intubated critically ill adult patients.MethodsIt is a four-center prospective observational study. Microaspiration biomarkers (pepsin and salivary amylase) concentrations were quantitatively measured on tracheal aspirates drawn before and after TEE. The primary endpoint was the percentage of patients with TEE-associated microaspiration, defined as: (1) ≥ 50% increase in biomarker concentration between pre-TEE and post-TEE samples, and (2) a significant post-TEE biomarker concentration (> 200 μg/L for pepsin and/or > 1685 IU/L for salivary amylase). Secondary endpoints included the development of VAP within three days after TEE and the evolution of tracheal cuff pressure throughout TEE.ResultsWe enrolled 100 patients (35 females), with a median age of 64 (53–72) years. Of the 74 patients analyzed for biomarkers, 17 (23%) got TEE-associated microaspiration. However, overall, pepsin and salivary amylase levels were not significantly different between before and after TEE, with wide interindividual variability. VAP occurred in 19 patients (19%) within 3 days following TEE. VAP patients had a larger tracheal tube size and endured more attempts of TEE probe introduction than their counterparts but showed similar aspiration biomarker concentrations. TEE induced an increase in tracheal cuff pressure, especially during insertion and removal of the probe.ConclusionsWe could not find any association between TEE-associated microaspiration and the development of VAP during the three days following TEE in intubated critically ill patients. However, our study cannot formally rule out a role for TEE because of the high rate of VAP observed after TEE and the limitations of our methods.