bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Presence of Exons (DPE): Sequencing Liquid Biopsy by NGS. A New Method for Clustering Colorectal Cancer Patients.
Authors: Rubio-Mangas David , García-Arranz Mariano , Torres-Rodriguez Yaima , León-Arellano Miguel , Suela-Rubio Javier , García-Olmo Damián 
Published: October 2022

Abstract
Differential presence of exons (DPE) by next generation sequencing (NGS) is a method of interpretation of whole exome sequencing. This method has been proposed to design a predictive and diagnostic algorithm with clinical value in plasma from patients bearing colorectal cancer (CRC). The aim of the present study was to determine a common exonic signature to discriminate between different clinical pictures, such as non-metastatic, metastatic and non-disease (healthy), using a sustainable and novel technology in liquid biopsy. Through DPE analysis, we determined the differences in DNA exon levels circulating in plasma between patients bearing CRC vs. healthy, patients bearing CRC metastasis vs. non-metastatic and patients bearing CRC metastasis vs. healthy comparisons. We identified a set of 510 exons (469 up and 41 down) whose differential presence in plasma allowed us to group and classify between the three cohorts. Random forest classification (machine learning) was performed and an estimated out-of-bag (OOB) error rate of 35.9% was obtained and the predictive model had an accuracy of 75% with a confidence interval (CI) of 56.6–88.5. In conclusion, the DPE analysis allowed us to discriminate between different patho-physiological status such as metastatic, non-metastatic and healthy donors. In addition, this analysis allowed us to obtain very significant values with respect to previous published results, since we increased the number of samples in our study. These results suggest that circulating DNA in patient’s plasma may be actively released by cells and may be involved in intercellular communication and, therefore, may play a pivotal role in malignant transformation (genometastasis).
Informed consent in randomised controlled trials: further development and evaluation of the Participatory and Informed Consent (PIC) measure
Authors: Wade Julia , Humphrys Elka , Realpe Alba , Gaunt Daisy , Burt Jenni 
Published: October 2022

Abstract

Background
Informed consent is an accepted ethical and legal prerequisite for trial participation, yet there is no standardised method of assessing patient understanding for informed consent. The Participatory and Informed Consent (PIC) measure was developed for application to recruitment discussions, to evaluate recruiter information provision and evidence of patient understanding. Preliminary evaluation of the PIC indicated the need to improve inter-rater and intra-rater reliability ratings and conduct further psychometric evaluation. This paper describes the assessment, revision and evaluation of the PIC within the context of OPTiMISE, a pragmatic primary care-based trial.
Methods
This study used multiple methods across two phases. In phase one, one researcher applied the existing PIC measure to 18 audio recorded recruitment discussions from the OPTiMISE study and made detailed observational notes about any uncertainties in application. Appointments were sampled to be maximally diverse for patient gender, study centre, recruiter and before and after an intervention to optimise information provision. Application uncertainties were reviewed by the study team, revisions made, and a coding manual developed and agreed. In phase two, the coding manual was used to develop tailored guidelines for applying the PIC to appointments within the OPTiMISE trial. Two researchers then assessed 27 further appointments, purposively sampled as above, to evaluate inter-rater and intra-rater reliability, content validity and feasibility.
Results
Application of the PIC to 18 audio recorded OPTiMISE recruitment discussions resulted in harmonisation of the scales rating recruiter information provision and evidence of patient understanding, minor amendments to clarify wording, and the development of detailed generic coding guidelines for applying the measure within any trial. Application of the revised measure using these guidelines to 27 further recruitment discussions showed good feasibility (time to complete), content validity (completion rate) and reliability (inter- and intra-rater) of the measure.
Conclusion
The PIC provides a means to evaluate the content of information provided by recruiters, patient participation in recruitment discussions and, to some extent, evidence of patient understanding. Future work will use the measure to evaluate recruiter information provision and evidence of patient understanding both across and within trials.
Outcomes of cesarean myomectomy via trans-endometrial approach in women with single intramural fibroid in the posterior uterine wall
Authors: Wang Qi , Lin Jinxiao , Dai Yan 
Published: October 2022

Abstract
Purpose: To evaluate the feasibility and effectiveness of cesarean myomectomy (CM) via trans-endometrial approach in pregnant women with single intramural fibroid in the posterior uterine wall.
Methods: Ninety-eight patients with single intramural fibroids in the posterior uterine wall who underwent CM were divided into two groups depending on surgical style. The study group consisted of 50 patients who underwent trans-endometrial myomectomy (EM), whereas the control group included 48 patients who had trans-serosal myomectomy (SM). Patients’ demographic data, intraoperative and postoperative outcomes were analyzed retrospectively.
Results: No significant differences were found in the demographic data, characteristics of fibroids (size, location and pathological type), intraoperative hemorrhage, blood transfusion rate, postoperative fever incidence and postoperative hospitalization between two groups (all p > 0.05). The time of operation and postoperative ventilation in the EM group was shorter than that in the SM group (p<0.05). More importantly, estimated blood loss and postoperative hemoglobin decline were less in the EM group than in the SM group (p<0.05).
Conclusion EM can be considered a viable procedure in CM for single intramural fibroids in posterior wall, with the benefit of shorter operative time ,less intraoperative bleeding and potentially reduced risk of pelvic adhesions.
Arsenic adsorption by functionalized polystyrene microplastics: kinetics and mechanisms
Authors: Mamtimin Xiringvl , Song Wei , Wang Yun , Habibul Nuzahat 
Published: October 2022

Abstract
We investigate adsorption characteristics of As(III) and As(V) onto two different functionalized polystyrene (PS) microplastics (MPs). Our results show that there is the potential for PS MPs to adsorb both As(III) and As(V). Using a particle size of 80–82 nm, maximum As(III) and As(V) adsorption capacities of 0.57 mg/g and 0.37 mg/g were obtained by PS-COOH MPs. These capacities were markedly higher than those for PS-NH2 MPs, which were 0.409 mg/g and 0.27 mg/g, respectively. The pseudo-second-order adsorption kinetics and Langmuir isotherm model indicates that hydrogen binding, hydroxyl complexation and electrostatic forces are the key mechanisms controlling adsorption. Adsorption capacity markedly decreases with increasing salinity or presence of humic acid (HA), suggesting an inhibiting effect of salinity and HA through outer-sphere complexation. These findings confirm that microplastics have great potential to adsorb As and hence are ultimately highly likely to affect the environmental behavior of As in an ecosystem.
Caesarean scar pregnancy - Is there a light in the end of the tunnel?
Authors: Shiber Yair , Maymon Ron , Gal-Kochav Maayan , Kugler Nadav , Pekar-Zlotin Marina , Smorgick Noam , Vaknin Zvi 
Published: October 2022

Abstract
Purpose: to summarize and present a single tertiary center’s 25 years of experience managing patients with caesarean scar pregnancies and their long term reproductive and obstetric outcomes.
Methods: A 25-year retrospective study included women diagnosed with CSP from 1996 to 2020 in one tertiary center. Data were retrieved from the medical records and through a telephone interview. Diagnosis was made by sonography and color Doppler. Treatments included methotrexate, suction curettage, hysteroscopy, embolization and wedge resection by laparoscopy or laparotomy as a function of the clinical manifestations, the physicians’ decisions, patient counseling, and parental requests.
Results: Analysis of the records recovered 60 cases of CSP (two of whom were recurrent). All patients had complete resolution with no indication for hysterectomy. Thirty-five patients had a long-term follow-up, of whom 24 (68.6%) attempted to conceive again and 22 (91.6%) succeeded. There were 17/22 (77.3%) patients with at least one live birth, 3/22 (13.6%) spontaneous miscarriages and 2/22 (9%) recurrent CSP. The obstetric complications included abnormal placentation 5/19 (26.3%), premature rupture of membranes 2/19 (10.5%), preterm delivery 4/19 (21%) and abnormality of the uterine scar 2/19 (10.5%). There was one case of neonatal death due to complications of prematurity 1/19 (5.2%).
Conclusion: CSP treatment focusing on reducing morbidity and preserving fertility has favorable long term reproductive and obstetric outcomes. In subsequent pregnancies, we recommend performing an early first trimester vaginal scan to map the location of the new pregnancy, followed by close monitoring given the obstetric complications mentioned above.
Factors associated with the grief among family caregivers of patients with dementia in China
Authors: WU JUNXIAN , SHEN QIN , LIU YU JING , XU YU , CHEN YUANYUAN 
Published: October 2022

Abstract
The current study aimed to investigate the influencing factors of grief in family caregivers of patients with dementia in China. In this cross-sectional study, 202 patients with dementia and their family caregivers were surveyed with demographic questionnaire, Caregiver Burden Inventory, Neuropsychiatric Inventory Questionnaire, and Marwit-Meuser Caregiver Grief Inventory Short Form. Through multivariate linear regression analysis, we identified the influencing factors of grief. Our results showed that the scores of caregiver grief were 59.46(SD=21.10); most family caregivers experienced grief; gender of caregivers, co-residency with the patient, behavioral and psychological symptoms of dementia and caregiver burden were the main factors associated with caregiver grief; and male and female caregivers experienced different types of caregiver burden. Future research will target nursing interventions and community services to reduce the burden and grief of caregivers of patients with dementia.
Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
Authors: Dufour Antoine , Das Nabangshu , de Almeida Luiz , Derakhshani Afshin , Young Daniel , Salo Paul , Rezansoff Alexander , Jay Gregory , Sommerhoff Christian , Schmidt Tannin , Krawetz Roman 
Published: October 2022

Abstract
Proteoglycan 4 (PRG4) is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis (OA). We found that mast cell tryptase β cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 resulted in a reduction of lubrication. Compared to full-length, cleaved PRG4 was shown to further activate NF-κB expression in cells overexpressing TLR2, -4, and − 5. In the destabilization of the medial meniscus (DMM) model of OA in rat, tryptase β and PRG4 colocalized at the site of injury in knee cartilage and were associated with disease severity. Human primary synovial fibroblasts from OA patients or non-OA healthy subjects treated with tryptase β and/or PRG4 were subjected to a quantitative shotgun proteomics and proteome changes were characterized, further supporting the role of NF-κB activation. We identified tryptase β as a modulator of joint lubrication in OA via the cleavage of PRG4.
A stability observer for human-robot and environment-robot interaction with variable admittance control
Authors: Wang Longxiang , Chen Chin-Yin , Wang Chongchong , Ying Kaichen , Li Yanbiao , Yang Guilin 
Published: October 2022

Abstract
When interacting with the environment or human, the robot is prone to unstable oscillation if the stiffness of the environment or human increases suddenly. In human-robot interaction, traditional frequency-based stability observers are easily impacted by the high-frequency signal noises or filter phase error, which may cause misdiagnosis. In environment-robot interaction, adaptive algorithm keeps the contact force stable by identifying the environmental stiffness, but the varying environmental stiffness may cause the failure of the adaptive algorithm. Therefore, this paper proposes an improved observer using the ratio of the force standard deviation to the maximum allowable force to eliminate the effect of high-frequency noises and alleviate the misdiagnosis. Moreover, we use the designed stability observer to monitor the interaction forces in real time and ensure the stable operation of the adaptive algorithm by updating the initial environmental stiffness. And we design a variable admittance control algorithm based on the stability observer to ensure the stability of the interaction. The final experimental results show that the stability observer and the corresponding control algorithm designed in this paper have better accuracy and robustness in human-robot and environment-robot interaction.
A Randomized, Double-blind, Placebo-controlled Pilot Trial of Low-intensity Pulsed Ultrasound Therapy for Refractory Angina Pectoris
Authors: Shindo Tomohiko , Ito Kenta , Ogata Tsuyoshi , Kurosawa Ryo , Eguchi Kumiko , Kagaya Yuta , Hanawa Kenichiro , Hasebe Yuhi , Nishimiya Kensuke , Shiroto Takashi , Takahashi Jun , Okumura Yasuo , Noguchi Teruo , Ozaki Yukio , Daida Hiroyuki , Hagiwara Nobuhisa , Masuyama Tohru , Chikamori Taishiro , Fukumoto Yoshihiro , Tsujita Kenichi , Kanai Hiroshi , Yasuda Satoshi , Shimokawa Hiroaki 
Published: October 2022

Abstract
Despite the advances in the treatment of cardiovascular diseases, effective treatment remains to be established to improve the quality of life of patients with chronic coronary syndrome. The aim of this study was to evaluate the effectiveness and safety of the low-intensity pulsed ultrasound (LIPUS) therapy, which we have developed as a novel non-invasive angiogenic therapy. We conducted a randomized, double-blind, placebo-controlled (RCT) pilot trial of the LIPUS therapy for patients with refractory angina pectoris without indication for PCI or CABG despite optimal medical therapy. The primary endpoint, the changes in weekly use of nitroglycerin were comparable; -3.06 (95% CI: -4.481 to -1.648) in the LIPUS group and − 3.10 (95% CI: -4.848 to -1.356) in the placebo group (both P < 0.01). In the present study, the LIPUS therapy did not further ameliorate chest pain as compared with optimal medications alone in patients with refractory angina pectoris (Registration ID: UMIN000012369).
The legacy of one hundred years of climate change for organic carbon stocks in global agricultural topsoils
Authors: Poeplau Christopher , Dechow Rene 
Published: October 2022

Abstract
Soil organic carbon (SOC) of agricultural soils is observed to decline in many parts of the world. For tearing apart management and climate change effects, the latter needs to be estimated comprehensively. In this study, an established FAO framework was used to model global agricultural topsoil SOC stock dynamics from 1919 to 2018 as attributable to climate change. On average, global agricultural topsoils lost 2.5±2.3 Mg C ha-1 with constant net primary production (NPP) or 1.6±3.4 Mg C ha-1 when NPP was modified by temperature and precipitation. Regional variability could be explained by the complex patterns of changes in temperature and moisture, as well as initial SOC stocks. However, average SOC losses have been an intrinsic and persistent feature of climate change in all climatic zones. This needs to be taken into consideration in reporting or accounting frameworks and halted in order to mitigate climate change and secure soil health.
Are B12 and B9 Deficiencies Independently Linked to Cardiovascular Biomarkers? Insights from a Cross-Sectional Analysis
Authors: Ghayad Jean Pierre , Barakett-Hamadé Vanda , Sleilaty Ghassan 
Published: October 2022

Abstract
Backgrounds/Objectives:
The effect of cobalamin and folate deficiency on cardiovascular disease is still unclear. We assessed the association of cobalamin and folate deficiency on lipidic and non-lipidic markers of cardiovascular disease in a large laboratory database.
Subjects/Methods:
We conducted a cross-sectional study on a large database of a tertiary hospital’s laboratory information system between 2017 and 2022. The study included laboratory data of Lebanese outpatients and cardiology inpatients. The following biological assays on serum were used: cobalamin, folate, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, creatinine, glycated hemoglobin, ferritin, C-reactive protein, fibrinogen, uric acid and homocysteine. Age, gender and a surrogate for cardiovascular disease were also used. Odds ratios adjusted for age, gender, inflammatory biomarkers and vitaminic status were derived using separate logistic regression models.
Results:
A total of 20,836 observations were included, of which 2.0% presented clinical cobalamin deficiency. The effect of cobalamin and folate deficiencies, while significantly affected cardiovascular biomarkers in univariate analyses, disappeared after adjusting on age, gender and inflammation biomarkers.
Conclusion:
In this exploratory analysis, cobalamin and folate deficiencies were not significantly associated with abnormal lipid values and non-lipidic markers of cardiovascular disease.
Pemetrexed induces ROS generation and cellular senescence by attenuating TS-mediated thymidylate metabolism to reverse gefitinib resistance in non-small cell lung cancer
Authors: Guo Renhua , Chen Yun , Zhang Chen , Jin Shidai , Li Jun , Dai Jiali , Zhang Zhihong 
Published: October 2022

Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are strongly recommended for non-small cell lung carcinoma (NSCLC) patients harboring active EGFR mutations, while drug resistance inevitably makes exploring the resistance mechanisms and seeking effective therapeutic strategies urgent endeavors. Thymidylate synthetase (TYMS or TS) is a dominant enzyme in thymidylate nucleotide metabolism. In this study, based on public database analysis and examination of gene sets from 140 NSCLC patients that received EGFR-TKI therapy, we found a significantly positive correlation between TS expression and overall survival (OS) and disease-free survival (DFS) in lung adenocarcinoma. Twenty-four tissue specimens from NSCLC patients exhibited upregulated TS mRNA expression in NSCLC patients resistant to gefitinib. The human NSCLC cell line PC9, which is sensitive to gefitinib, and relatively resistant PC9/GR cells were used to demonstrate that knockdown of TS restored the sensitivity of resistant cells to gefitinib. Furthermore, pemetrexed effectively suppressed TS-mediated thymidylate metabolism and induced ROS generation and cellular senescence, thereby hampering carcinogenesis and restoring cell sensitivity to gefitinib. The combination of pemetrexed and gefitinib damaged the proliferation, migration and invasion capabilities of gefitinib-resistant cells, exhibiting a synergistic anticancer effect. Our findings illuminate the potential mechanism of TS-triggered gefitinib resistance and indicate that inhibition of TS by pemetrexed can potentiate the effect of gefitinib in NSCLC cells resistant to gefitinib. Pemetrexed combined with gefitinib has potent anti-progression potential in gefitinib-resistant NSCLC. This suggests that NSCLC patients with both high TS expression and EGFR-driving mutations might benefit more from a combination strategy of EGFR-TKIs and pemetrexed-based chemotherapy than EGFR-TKI monotherapy, which has profound clinical implications and considerable therapeutic value.
The distribute impact of labour market and cash transfer policies during the COVID-19 pandemic in Latin America
Authors: Beccaria Luis , Maurizio Roxana , Martinez SIlvana 
Published: October 2022

Abstract
The COVID-19 pandemic has generated an unprecedented economic, health, labour and social crisis in the world. Latin America is one of the regions that has been most strongly affected. The main aim of this paper is to assess the dynamics of family income inequality and its components since the onset of the pandemic in six Latin American countries -Argentina, Brazil, Colombia, Costa Rica, Peru and Uruguay-. The unequalizing impact of the worsening of the labour market during the contraction phase was mainly associated with the significant loss of informal, low-paid, jobs. This effect was offset, at least partially, by the equalizing role of cash transfers policies put in place in the outbreak of the pandemic. An opposite impact of these income sources appears during the recovery phase, as most countries gradually reduced or stopped those transfers as employment and, therefore, labour incomes partially recovered. Nearly two years into the COVID-19 pandemic inequality is higher than 2019 in almost all countries studied exacerbating existing high-income gaps in one of the world's most unequal regions.
A nomogram risk assessment model to predict the possibility of type II endoleak-related re- intervention after endovascular aneurysm repair (EVAR)
Authors: Liu Zongwei , Chen Yonghui , Qin Yafei , Bi Jiaxue , Wang Jiaxin , Niu Fang , Dai Xiangchen 
Published: October 2022

Abstract
Purpose
This study aimed to develop and validate a novel nomogram risk assessment model to predict the possibility of type II endoleak (T2EL)-related re-intervention.
Methods and materials:
The data of 455 patients with abdominal aortic aneurysms who underwent elective endovascular aneurysm repair (EVAR) procedures between January 2018 and December 2021 at our single center were retrospectively reviewed. Following the implementation of exclusion criteria, 283 patients were finally included and divided into T2EL-related re-intervention (n = 42) and non-T2EL (n = 241) groups.
Results
The overall T2EL-related re-intervention rate for 283 patients was 14.8% (42/283). Using multivariate analysis, significant risk factors for re-intervention included age (OR, 1.104; 95% CI, 1.023–1.191; P = 0.011), smoking (OR, 4.249; 95% CI, 1.383–13.052; P = 0.012), hypertension (OR, 4.175; 95% CI, 1.321–13.192; P = 0.015), and number of patent lumbar arteries (OR, 6.270; 95% CI, 3.030–12.974; P < 0.001). The discrimination ability of this risk-predictive model was reasonable (concordance index [C-index] = 0.886; 95% CI, 0.825–0.947). The Hosmer-Lemeshow goodness of fit test was performed on the model, and the chi-square value was 13.832 (P = 0.086), presenting an excellent agreement between the model-predicted and observed values. The receiver operating characteristic (ROC) curve identified that the risk thresholds of re-intervention were a diameter of > 2.77 mm for the diameter of the inferior mesenteric artery and a proportion of < 45.5% for thrombus volume in the aneurysm sac.
Conclusion
This novel nomogram risk assessment model for predicting the possibility of patients’ T2EL-related re-interventions after EVAR should be helpful in discriminating high-risk patients. Two novel risk thresholds may imply a higher possibility of T2EL-related re-intervention after EVAR.
A State-of-the-Art Technique for Malware Detection Based on Deep Learning in IoT Environment
Authors: ALI MUHAMMAD MUMTAZ , ZHENFEI WANG , WEIYAN HOU , SHAUKAT ZEESHAN , SHABBIR AYESHA , RASHEED AQSA , MAQSOOD FAIQA , ZIA QASIM , REHMAN HAMEED UR 
Published: October 2022

Abstract
The authors have requested that this preprint be removed from Research Square.