bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature-dependent tensile properties of polyamide 12 for the use in percutaneous transluminal coronary angioplasty balloon catheters
Authors: Amstutz C. , Weisse B. , Valet S. , Haeberlin A. , Burger J. , Zurbuchen A. 
Published: October 2021

Abstract
Background
Percutaneous transluminal coronary angioplasty (PTCA) balloon catheters must withstand high pressures required for the lesion treatment, pushing loads during insertion, and pulling loads during withdrawal. These loads pose a challenge especially for polymeric tubular shafts with small cross sections. In order to enable new design innovations and to better understand the mechanics of current catheter technologies, the tensile properties of polyamide (PA) 12 were investigated. PA 12 dog bone specimens and medical PA 12 tubes were either stored at ambient temperature and humidity or conditioned in water, and subjected to tensile loads at different temperatures. In addition, the effect on the tensile properties of the necking process, a forming process to reduce the wall thickness of the tubes, was determined.

Results
The tested tubes showed a reduction in both Young’s Modulus (− 41.5%) and yield stress (− 29.2%) compared to standardized specimens. Furthermore, an increase in temperature and water absorption softens the material and reduces the mechanical properties like the Young’s Modulus and the yield stress. It was found that the material strengthens during the necking process. Likely due to the orientation of the polymers chain molecules in load direction (Rösler et al., 2007), the Young’s Modulus of the material could be increased by 43.5%. Furthermore, the absence of a yield point after necking allows for a greater loading capacity of the material without unstable neck growth. Besides the strengthening, the ultimate strain is reduced by 50%. This indicates that the necking process induces plastic deformation.

Conclusion
The investigation showed that the environmental conditions like temperature and humidity can influence mechanical properties. It could also be shown that pre-forming processes such as necking can enhance the mechanical properties, such as the Young’s Modulus, while reducing the wall thickness. These findings suggest possible further development of catheters with a small cross section and higher mechanical strength and highlight the importance to account for the targeted operating temperature during the design process.
Identification and validation of an immune-associated RNA-binding proteins signature to predict clinical outcomes and therapeutic responses in colon cancer patients
Authors: Sun Di , Yang Kui-Sheng , Chen Jian-Liang , Wang Zheng-bing 
Published: October 2021

Abstract
Background
The immune infiltration of patients with colon cancer (CC) is closely associated with RNA-binding proteins (RBPs). However, immune-associated RBPs (IARBPs) in CC remain unexplored.

Methods
The data were downloaded from The Cancer Genome Atlas (TCGA) and the patients were divided into four immune subgroups by single sample gene set enrichment analysis (ssGSEA), in which weighted gene correlation network analysis (WGCNA) identified modules of co-expressed genes correlated with immune infiltration. Univariate (UCR) and multivariate Cox regression (MCR) analyses were applied to screen survival-associated IARBPs. Then, a prognostic signature was performed on TCGA dataset. Risk model was constructed based on the TCGA dataset. Based on the median risk score, CC patients were subdivided into low- and high-risk groups. Furthermore, the accuracy and prognostic value of this signature were validated by using Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC). We further validated the findings in Gene Expression Omnibus (GEO) database. Finally, we evaluated the association between gene expression level and drug sensitivity.

Results
Based on the infiltration of immune cells, the TCGA patients were divided into four subgroups. In total, we identified 25 IARBPs, after differential expression and WGCNA analysis. Subsequently, two IARBP signatures (FBXO17 and PPARGC1A) were identified to be significantly associated with the overall survival (OS) of CC patients. K-M survival analysis revealed that the low-risk group correlated with prolonged OS. The prognostic signature was an independent prognostic factor and reflects the immune status of CC patients. Finally, FBXO17 was related with drug sensitivity of bleomycin, gemcitabine, and lenvatinib. PPARGC1A was related to drug sensitivity of dabrafenib, vemurafenib, and trametinib.

Conclusion
A novel two immune-associated RBPs that was established that may be useful in predicting survival and individualized treatment.
Improving outcomes of liver resection for hepatocellular carcinoma associated with portal vein tumor thrombosis over the evolving eras of treatment
Authors: Wang Yu-Chao , Lee Jin-Chiao , Wu Tsung-Han , Cheng Chih-Hsien , Lee Chen-Fang , Wu Ting-Jung , Chou Hong-Shiue , Chan Kun-Ming , Lee Wei-Chen 
Published: October 2021

Abstract
Background
The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment.

Materials and methods
A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined.

Results
Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months.

Conclusion
The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.
How to measure premature mortality? A proposal combining “relative” and “absolute” approaches
Authors: Mazzuco Stefano , Suhrcke Marc , Zanotto Lucia 
Published: October 2021

Abstract
Background
The concept of “premature mortality” is at the heart of many national and global health measurement and benchmarking efforts. However, despite the intuitive appeal of its underlying concept, it is far from obvious how to best operationalise it. The previous work offers at least two basic approaches: an absolute and a relative one. The former—and far more widely used— approach sets a unique age threshold (e.g. 65 years), below which deaths are defined as premature. The relative approach derives the share of premature deaths from the country-specific age distribution of deaths in the country of interest. The biggest disadvantage of the absolute approach is that of using a unique, arbitrary threshold for different mortality patterns, while the main disadvantage of the relative approach is that its estimate of premature mortality strongly depends on how the senescent deaths distribution is defined in each country.

Method
We propose to overcome some of the downsides of the existing approaches, by combining features of both, using a hierarchical model, in which senescent deaths distribution is held constant for each country as a pivotal quantity and the premature mortality distribution is allowed to vary across countries. In this way, premature mortality estimates become more comparable across countries with similar characteristics.

Results
The proposed hierarchical models provide results, which appear to align with related evidence from specific countries. In particular, we find a relatively high premature mortality for the United States and Denmark.

Conclusions
While our hybrid approach overcomes some of the problems of previous measures, some issues require further research, in particular the choice of the group of countries that a given country is assigned to and the choice of the benchmarks within the groups. Hence, our proposed method, combined with further study addressing these issues, could provide a valid alternative way to measure and compare premature mortality across countries.
The role of PDGFRA as a therapeutic target in young colorectal cancer patients
Authors: Kim Tae Won , Hong Hye Kyung , Lee Chung , Kim Sunmin , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol , Huh Jung Wook , Park Yoon Ah , Joung Je-Gun , Park Woong-Yang , Cho Yong Beom 
Published: October 2021

AbstractBackgroundYoung patients with colorectal cancer (CRC) exhibit poor prognoses compared to older patients due to the difficulty in early diagnosis and treatment. However, the underlying molecular characteristics are still unclear.MethodsWe conducted a comprehensive analysis of 49 CRC patients without hereditary CRC using the whole-exome and RNA sequencing with tumor and matched normal samples. A total of 594 TCGA samples and 4 patient-derived cells were utilized for validation.ResultsConsensus molecular subtype 4 (CMS4) (53.85%) and CMS2 (38.46%) were enriched in the young (≤ 40 years) and old (> 60 years) age groups, respectively. A CMS4-associated gene, platelet-derived growth factor receptor α (PDGFRA), was significantly upregulated in young patients with CRC (FC = 3.21, p = 0.0001) and was negatively correlated with age (p = 0.0001, R = − 0.526). Moreover,PDGFRAshowed a positive co-expression with metastasis-related genes in young CRC patients. In vitro validation confirmed that young patient-derived cells (PDCs) showed an enriched expression ofPDGFRAcompared to old PDCs and a reduced proliferation rate by knockdown ofPDGFRA. Furthermore, young CRC patients were more sensitive to regorafenib, a PDGFRA-targeting drug, than old CRC patients.ConclusionsOur study suggests that CRC in young patients is associated with CMS4 and PDGFRA. In addition, PDGFRA may serve potential of novel therapeutic strategies and represent a predictive biomarker of response to regorafenib for young CRC patients.
Cytotoxic lymphocytes-related gene ITK from a systematic CRISPR screen could predict prognosis of ovarian cancer patients with distant metastasis
Authors: Xu Mengyao , Huang Shan , Chen Jiahui , Xu Wanxue , Xiang Rong , Piao Yongjun , Zhao Shuangtao 
Published: October 2021

Abstract
Background
Ovarian cancer, a highly metastatic malignancy, has benefited tremendously from advances in modern human genomics. However, the genomic variations related to the metastasis remains unclear.

Methods
We filtered various significant genes (n = 6722) associated with metastasis within a large-scale functional genomic CRISPR/Cas9 knock-out library including 122,756 single guide RNAs, and identified ITK (IL2 Inducible T Cell Kinase) as a potential cancer suppressor gene for ovarian cancer metastasis. Downstream bioinformatic analysis was performed for ITK using public databases.

Results
We found that patients in low-ITK group had poor prognosis and more distant metastasis than those in high-ITK group in TCGA and GEO databases. We also demonstrated that ITK combined with the clinical factors could accurately predict prognosis through multiple Cox regression analysis and ROC analysis. Moreover, alterations correlated with distant metastasis emereged with significantly increased expression in SAMRCD1 in low-ITK group, but CD244 and SOCS1 in high-ITK group. Integrated analysis revealed dysregulated molecular processes including predominantly oncogenic signaling pathways in low-ITK group but immune related pathways in high-ITK group, which suggested ITK might inhibit distant metastasis in ovarian cancer. Furtherly, deconvolution of the cellular composition of all samples validated the close correlation between ITK and immune related function especially for cytotoxic lymphocytes.

Conclusions
Together, these data provide insights into the potential role of ITK, with implications for the future development of tansformative ovarian cancer therapeutics.
Ribonuclease zymogen induces cytotoxicity upon HIV-1 infection
Authors: Windsor Ian W. , Dudley Dawn M. , O’Connor David H. , Raines Ronald T. 
Published: October 2021

AbstractBackgroundTargeting RNA is a promising yet underdeveloped modality for the selective killing of cells infected with HIV-1. The secretory ribonucleases (RNases) found in vertebrates have cytotoxic ribonucleolytic activity that is kept in check by a cytosolic ribonuclease inhibitor protein, RI.MethodsWe engineered amino acid substitutions that enable human RNase 1 to evade RI upon its cyclization into a zymogen that is activated by the HIV-1 protease. In effect, the zymogen has an HIV-1 protease cleavage site between the termini of the wild-type enzyme, thereby positioning a cleavable linker over the active site that blocks access to a substrate.ResultsThe amino acid substitutions in RNase 1 diminish its affinity for RI by 106-fold and confer high toxicity for T-cell leukemia cells. Pretreating these cells with the zymogen leads to a substantial drop in their viability upon HIV-1 infection, indicating specific toxicity toward infected cells.ConclusionsThese data demonstrate the utility of ribonuclease zymogens as biologic prodrugs.
Smoothness metrics for reaching performance after stroke. Part 1: which one to choose?
Authors: Mohamed Refai Mohamed Irfan , Saes Mique , Scheltinga Bouke L. , van Kordelaar Joost , Bussmann Johannes B. J. , Veltink Peter H. , Buurke Jaap H. , Meskers Carel G. M. , van Wegen Erwin E. H. , Kwakkel Gert , van Beijnum Bert-Jan F. 
Published: October 2021

AbstractBackgroundSmoothness is commonly used for measuring movement quality of the upper paretic limb during reaching tasks after stroke. Many different smoothness metrics have been used in stroke research, but a ‘valid’ metric has not been identified. A systematic review and subsequent rigorous analysis of smoothness metrics used in stroke research, in terms of their mathematical definitions and response to simulated perturbations, is needed to conclude whether they are valid for measuring smoothness. Our objective was to provide a recommendation for metrics that reflect smoothness after stroke based on: (1) a systematic review of smoothness metrics for reaching used in stroke research, (2) the mathematical description of the metrics, and (3) the response of metrics to simulated changes associated with smoothness deficits in the reaching profile.MethodsThe systematic review was performed by screening electronic databases using combined keyword groupsStroke,ReachingandSmoothness. Subsequently, each metric identified was assessed with mathematical criteria regarding smoothness: (a) being dimensionless, (b) being reproducible, (c) being based on rate of change of position, and (d) not being a linear transform of other smoothness metrics. The resulting metrics were tested for their response to simulated changes in reaching using models of velocity profiles with varying reaching distances and durations, harmonic disturbances, noise, and sub-movements. Two reaching tasks were simulated; reach-to-point and reach-to-grasp. The metrics that responded as expected in all simulation analyses were considered to be valid.ResultsThe systematic review identified 32 different smoothness metrics, 17 of which were excluded based on mathematical criteria, and 13 more as they did not respond as expected in all simulation analyses. Eventually, we found that, for reach-to-point and reach-to-grasp movements, onlySpectral Arc Length(SPARC) was found to be a valid metric.ConclusionsBased on this systematic review and simulation analyses, we recommend the use of SPARC as a valid smoothness metric in both reach-to-point and reach-to-grasp tasks of the upper limb after stroke. However, further research is needed to understand the time course of smoothness measured with SPARC for the upper limb early post stroke, preferably in longitudinal studies.
Insights into motor performance deficits after stroke: an automated and refined analysis of the lower-extremity motor coordination test (LEMOCOT)
Authors: Handelzalts Shirley , Koren Yogev , Goldhamer Noy , Yeshurun-Tayer Adi , Parmet Yisrael , Shmuelof Lior , Bar-Haim Simona 
Published: October 2021

AbstractBackgroundThe lower-extremity motor coordination test (LEMOCOT) is a performance-based measure used to assess motor coordination deficits after stroke. We aimed to automatically quantify performance on the LEMOCOT and to extract additional performance parameters based on error analysis in persons with stroke (PwS) and healthy controls. We also aimed to explore whether these parameters provide additional information regarding motor control deficit that is not captured by the traditional LEMOCOT score. In addition, the associations between the LEMOCOT score, parameters of error and performance-based measures of lower-extremity impairment and gait were tested.MethodsTwenty PwS (age: 62 ± 11.8 years, time after stroke onset: 84 ± 83 days; lower extremity Fugl-Meyer: 30.2 ± 3.7) and 20 healthy controls (age: 42 ± 15.8 years) participated in this cross-sectional exploratory study. Participants were instructed to move their big toe as fast and accurately as possible between targets marked on an electronic mat equipped with force sensors (Zebris FDM-T, 60 Hz). We extracted the contact surface area of each touch, from which the endpoint location, the center of pressure (COP), and the distance between them were computed. In addition, the absolute and variable error were calculated.ResultsPwS touched the targets with greater foot surface and demonstrated a greater distance between the endpoint location and the location of the COP. After controlling for the number of in-target touches, greater absolute and variable errors of the endpoint were observed in the paretic leg than in the non-paretic leg and the legs of controls. Also, the COP variable error differentiated between the paretic, non-paretic, and control legs and this parameter was independent of in-target counts. Negative correlations with moderate effect size were found between the Fugl Meyer assessment and the error parameters.ConclusionsPwS demonstrated lower performance in all outcome measures than did controls. Several parameters of error indicated differences between legs (paretic leg, non-paretic leg and controls) and were independent of in-target touch counts, suggesting they may reflect motor deficits that are not identified by the traditional LEMOCOT score.
Postoperative acute kidney injury requiring continuous renal replacement therapy and outcomes after coronary artery bypass grafting: a nationwide cohort study
Authors: Oh Tak Kyu , Song In-Ae 
Published: October 2021

Abstract
Background
Previous studies reported that patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) after cardiac surgery were at a higher risk of postoperative mortality. However, the impact of AKI and CRRT on long-term mortality has not yet been identified. Therefore, we investigated whether postoperative AKI requiring CRRT was associated with one-year all-cause mortality after coronary artery bypass grafting (CABG).

Methods
For this population-based cohort study, we analyzed data from the National Health Insurance Service database in South Korea. The cohort included all adult patients diagnosed with ischemic heart disease who underwent isolated CABG between January 2012 and December 2017.

Results
A total of 15,115 patients were included in the analysis, and 214 patients (1.4%) required CRRT for AKI after CABG during hospitalization. They received CRRT at 3.1 ± 8.5 days after CABG, for 3.1 ± 7.8 days. On multivariable Cox regression, the risk of 1-year all-cause mortality in patients who underwent CRRT was 7.69-fold higher. Additionally, on multivariable Cox regression, the 30-day and 90-day mortality after CABG in patients who underwent CRRT were 18.20-fold and 20.21-fold higher than the normal value, respectively. Newly diagnosed chronic kidney disease (CKD) requiring renal replacement therapy (RRT) 1 year after CABG in patients who underwent CRRT was 2.50-fold higher. In the generalized log-linear Poisson model, the length of hospital stay (LOS) in patients who underwent CRRT was 5% longer.

Conclusions
This population-based cohort study showed that postoperative AKI requiring CRRT was associated with a higher 1-year all-cause mortality after CABG. Furthermore, it was associated with a higher rate of 30-day and 90-day mortality, longer LOS, and higher rate of CKD requiring RRT 1 year after CABG. Our results suggest that CRRT-associated AKI after CABG may be associated with an increased risk of mortality; hence, there should be interventions in these patients after hospital discharge.
Team approach to polypharmacy evaluation and reduction: study protocol for a randomized controlled trial
Authors: Mangin Dee , Lamarche Larkin , Agarwal Gina , Banh Hoan Linh , Dore Brown Naomi , Cassels Alan , Colwill Kiska , Dolovich Lisa , Farrell Barbara , Garrison Scott , Gillett James , Griffith Lauren E. , Holbrook Anne , Jurcic-Vrataric Jane , McCormack James , O’Reilly Daria , Raina Parminder , Richardson Julie , Risdon Cathy , Savelli Mat , Sherifali Diana , Siu Henry , Tarride Jean-Éric , Trimble Johanna , Ali Abbas , Freeman Karla , Langevin Jessica , Parascandalo Jenna , Templeton Jeffrey A. , Dragos Steven , Borhan Sayem , Thabane Lehana 
Published: October 2021

AbstractBackgroundPolypharmacy in older adults can be associated with negative outcomes including falls, impaired cognition, reduced quality of life, and general and functional decline. It is not clear to what extent these are reversible if the number of medications is reduced. Primary care does not have a systematic approach for reducing inappropriate polypharmacy, and there are few, if any, approaches that account for the patient’s priorities and preferences. The primary objective of this study is to test the effect of TAPER (Team Approach to Polypharmacy Evaluation and Reduction), a structured operationalized clinical pathway focused on reducing inappropriate polypharmacy. TAPER integrates evidence tools for identifying potentially inappropriate medications, tapering, and monitoring guidance and explicit elicitation of patient priorities and preferences. We aim to determine the effect of TAPER on the number of medications (primary outcome) and health-related outcomes associated with polypharmacy in older adults.MethodsWe designed a multi-center randomized controlled trial, with the lead implementation site in Hamilton, Ontario. Older adults aged 70 years or older who are on five or more medications will be eligible to participate. A total of 360 participants will be recruited. Participants will be assigned to either the control or intervention arm. The intervention involves a comprehensive multidisciplinary medication review by pharmacists and physicians in partnership with patients. This review will be focused on reducing medication burden, with the assumption that this will reduce the risks and harms of polypharmacy. The control group is a wait list, and control patients will be given appointments for the TAPER intervention at a date after the final outcome assessment. All patients will be followed up and outcomes measured in both groups at baseline and 6 months.DiscussionOur trial is unique in its design in that it aims to introduce an operationalized structured clinical pathway aimed to reduce polypharmacy in a primary care setting while at the same time recording patient’s goals and priorities for treatment.Trial registrationClinicalTrials.govNCT02942927. First registered on October 24, 2016.