bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suction force rather than aspiration flow correlates with recanalization in hard clots: an in vitro study model
Authors: Fernandez-Sanchez David , Garcia-Sabido Daniel , Jovin Tudor G , Villanova Helena , Andersson Tommy , Nogueira Raul G , Cognard Cristophe , Ribo Marc , Siddiqui Adnan H , Galve Iñaki , Arad Ofir , Salmon François 
Published: January 2021

BackgroundANA Advanced Neurovascular Access provides a novel funnel component designed to reduce clot fragmentation and facilitate retrieval in combination with stent-retrievers (SRs) in stroke patients by restricting flow and limiting clot shaving. In previous publications ANA presented excellent in vitro/in vivo efficacy data, especially with fibrin-rich hard clots. We aimed to determine the main physical property responsible for these results, namely suction force versus aspiration flow.MethodsWe evaluated in a bench model the suction force and flow generated by ANA and compared them to other neurovascular catheters combined with a SR (Solitaire). Aspiration flow was evaluated with a flow rate sensor while applying vacuum pressure with a pump. Suction force was determined using a tensile strength testing machine and a purposely designed tool that completely seals the device tip simulating complete occlusion by a hard clot. Suction force was defined as the force needed to separate the device from the clot under aspiration. All experiments were repeated five times, and mean values used for comparisons.ResultsAspiration flow increased with the inner diameter of the device: ANA 1.85±0.04 mL/s, ACE68 3.74±0.05 mL/s, and 8F-Flowgate2 5.96±0.30 mL/s (P<0.001). After introducing the SR, the flow was reduced by an average of 0.57±0.12 mL/s. Due to its larger distal surface, ANA suction force (1.69±0.40 N) was significantly higher than ACE68 (0.26±0.04 N) and 8F-Flowgate2 (0.42±0.06 N) (P<0.001). After introducing the SR, suction force variation was not relevant except for ANA that increased to 2.64±0.41 N.ConclusionDespite lower in vitro aspiration flow, the ANA design showed a substantially higher suction force than other thrombectomy devices.
Long-term ice-rich permafrost coast sensitivity to air temperatures and storm influence: lessons from Pullen Island, Northwest Territories, Canada
Authors: Berry H. Bay , Whalen Dustin , Lim Michael 
Published: January 2021

Response of erosive mechanisms to climate change is of mounting concern on Beaufort Sea coasts, which experience some of the highest erosion rates in the Arctic. Collapse of intact permafrost blocks and slumping within sprawling retrogressive thaw complexes are two predominant mechanisms that manifest as cliff retreat in this region. Using aerial imagery and ground survey data from Pullen Island, Northwest Territories., Canada, from 13 time points between 1947 and 2018, we observe increasing mean retreat rates from 0 ± 4.8 m a−1 in 1947 to 12 ± 0.3 m a−1 in 2018. Mean summer air temperature was positively correlated with cliff retreat over each time step via block failure (r2 = 0.08; p = 0.5) and slumping (r2 = 0.41; p = 0.05), as was mean storm duration with cliff retreat via block failure (r2 = 0.84; p = 0.0002) and slumping (r2 = 0.34; p = 0.08). These data indicate that air temperature has a greater impact in slump-dominated areas, whereas storm duration has greater control in areas of block failure. Increasingly, heterogeneous cliff retreat rates are likely resulting from different magnitudes of response to climate trends depending on mechanism, and on geomorphological variations that prescribe occurrences of retrogressive thaw slumps.
A Feature Driven Intelligent System for Neurodegenerative Disorder Detection: An Application on Speech Dataset for Diagnosis of Parkinson’s Disease
Authors: Cantürk İsmail 
Published: January 2021

Parkinson’s disease (PD) is a prevalent, and progressive neurological disorder. Due to the motor and non-motor symptoms of the disease, it lowers life quality of the patients. Tremor, rigidity, depression, anxiety etc. are among the symptoms. Clinical diagnosis of PD is usually based on appearance of motor features. Additionally, different empirical tests were proposed by scholars for early detection of the disease. It is known that people with PD have speech impairments. Therefore, voice tests are used for early detection of the disease. In this study, an automated machine learning system was proposed for high accuracy classification of the speech signals of PD patients. The system includes feature reduction methods and classification algorithms. Feature reductions and classifications were performed for all participants, males, and females separately. Contributions of feature sets to classification accuracy were discussed. Experimental results were evaluated with different performance metrics. The proposed system obtained state of the art results in all categories. We acquired better performances for gender based classifications.
Race and Patient-reported Symptoms in Adherence to Adjuvant Endocrine Therapy: A Report from the Women's Hormonal Initiation and Persistence Study
Authors: Sheppard Vanessa B. , Sutton Arnethea L. , Hurtado-de-Mendoza Alejandra , He Jun , Dahman Bassam , Edmonds Megan C. , Hackney Mary Helen , Tadesse Mahlet G. 
Published: January 2021

Abstract

Background:
Adjuvant endocrine therapy (AET) improves outcomes in women with hormone receptor–positive (HR+) breast cancer. Suboptimal AET adherence is common, but data are lacking about symptoms and adherence in racial/ethnic minorities. We evaluated adherence by race and the relationship between symptoms and adherence.

Methods:
The Women's Hormonal Initiation and Persistence study included women diagnosed with nonrecurrent HR+ breast cancer who initiated AET. AET adherence was captured using validated items. Data regarding patient (e.g., race), medication-related (e.g., symptoms), cancer care delivery (e.g., communication), and clinicopathologic factors (e.g., chemotherapy) were collected via surveys and medical charts. Multivariable logistic regression models were employed to calculate odds ratios and 95% confidence intervals (CIs) associated with adherence.

Results:
Of the 570 participants, 92% were privately insured and nearly one of three were Black. Thirty-six percent reported nonadherent behaviors. In multivariable analysis, women less likely to report adherent behaviors were Black (vs. White; OR, 0.43; 95% CI, 0.27–0.67; P &lt; 0.001) and with greater symptom burden (OR, 0.98; 95% CI, 0.96–1.00; P &lt; 0.05). Participants more likely to be adherent were overweight (vs. normal weight) (OR, 1.58; 95% CI, 1.04–2.43; P &lt; 0.05), sat ≤ 6 hours a day (vs. ≥6 hours; OR, 1.83; 95% CI, 1.25–2.70; P &lt; 0.01), and were taking aromatase inhibitors (vs. tamoxifen; OR, 1.91; 95% CI, 1.28–2.87; P &lt; 0.01).

Conclusions:
Racial differences in AET adherence were observed. Longitudinal assessments of symptom burden are needed to better understand this dynamic process and factors that may explain differences in survivor subgroups.

Impact:
Future interventions should prioritize Black survivors and women with greater symptom burden.
A Randomized Comparison of Different Vaginal Self-sampling Devices and Urine for Human Papillomavirus Testing—Predictors 5.1
Authors: Cadman Louise , Reuter Caroline , Jitlal Mark , Kleeman Michelle , Austin Janet , Hollingworth Tony , Parberry Anna L. , Ashdown-Barr Lesley , Patel Deepali , Nedjai Belinda , Lorincz Attila T. , Cuzick Jack 
Published: January 2021

Abstract

Background:
Human papillomavirus (HPV)-based screening is rapidly replacing cytology as the cervical screening modality of choice. In addition to being more sensitive than cytology, it can be done on self-collected vaginal or urine samples. This study will compare the high-risk HPV positivity rates and sensitivity of self-collected vaginal samples using four different collection devices and a urine sample.

Methods:
A total of 620 women referred for colposcopy were invited to provide an initial stream urine sample collected with the Colli-Pee device and take two vaginal self-samples, using either a dry flocked swab (DF) and a wet dacron swab (WD), or a HerSwab (HS) and Qvintip (QT) device. HPV testing was performed by the BD Onclarity HPV Assay.

Results:
A total of 600 vaginal sample pairs were suitable for analysis, and 505 were accompanied by a urine sample. Similar positivity rates and sensitivities for CIN2+ and CIN3+ were seen for DF, WD, and urine, but lower values were seen for QT and HS. No clear user preferences were seen between devices, but women found urine easiest to collect, and were more confident they had taken the sample correctly. The lowest confidence in collection was reported for HS.

Conclusions:
Urine, a DF swab, and WD swab all performed well and were well received by the women, whereas the Qvintip and HerSwab devices were less satisfactory.

Impact:
This is the first study to compare five self-sampling methods in the same women taken at the same time. It supports wider use of urine or vaginal self-sampling for cervical screening.
Dual Antiangiogenesis Agents Bevacizumab Plus Trebananib, without Chemotherapy, in First-line Treatment of Metastatic Colorectal Cancer: Results of a Phase II Study
Authors: Mooi Jennifer , Chionh Fiona , Savas Peter , Da Gama Duarte Jessica , Chong Geoffrey , Brown Stephen , Wong Rachel , Price Timothy J. , Wann Alysson , Skrinos Effie , Mariadason John M. , Tebbutt Niall C. 
Published: January 2021

AbstractPurpose:To assess the efficacy and safety of dual antiangiogenesis agents, bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer (mCRC).Patients and Methods:This open-label phase II study enrolled patients with unresectable mCRC with no prior systemic treatment. All patients received bevacizumab 7.5 mg/kg 3-weekly and trebananib 15 mg/kg weekly. The primary endpoint was disease control [stable disease, partial response (PR), or complete response (CR)] at 6 months (DC6m). Secondary endpoints included toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory biomarkers in plasma angiogenesis–related proteins, tumor gene expression, and plasma antibodies to tumor antigens were examined.Results:Forty-five patients were enrolled from four Australian sites. DC6m was 63% [95% confidence interval (CI), 47–77]. ORR was 17% (95% CI, 7–32), comprising of seven PRs. Median duration of response was 20 months (range, 10–48 months). Median PFS was 8.4 months and median OS 31.4 months. Grade 1–2 peripheral edema and joint-related symptoms were common. Overall incidence of grade 3–4 adverse events (AE) of any type was 33% (n = 15). Expected AEs of bevacizumab treatment did not appear to be increased by the addition of trebananib.Conclusions:In a first-line mCRC population, the dual antiangiogenic combination, bevacizumab plus trebananib, without chemotherapy, was efficacious with durable responses. The toxicity profile of the combination was manageable and did not exceed that expected with bevacizumab +/− chemotherapy. Exploratory biomarker results raise the hypothesis that the antiangiogenic combination may enable the antitumor immune response in immunotolerant colorectal cancer.
Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody
Authors: Harding James J. , Moreno Victor , Bang Yung-Jue , Hong Min Hee , Patnaik Amita , Trigo José , Szpurka Anna M. , Yamamoto Noboru , Doi Toshihiko , Fu Siqing , Calderon Boris , Velez de Mendizabal Nieves , Calvo Emiliano , Yu Danni , Gandhi Leena , Liu Zhuqing Tina , Galvao Violeta Regnier , Leow Ching Ching , de Miguel Maria J. 
Published: January 2021

Abstract

Purpose:
T-cell immunoglobulin and mucin-domain–containing molecule-3 (TIM-3) blunts anticancer immunity and mediates resistance to programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors. We assessed a novel, first-in-class, TIM-3 mAb, LY3321367, alone or in combination with the anti-PD-L1 antibody, LY300054 in patients with advanced solid tumor.

Patients and Methods:
This open-label, multicenter, phase Ia/b study aimed to define the safety/tolerability and recommended phase II dose (RP2D) of LY3321367 with or without LY300054. Secondary objectives included pharmacokinetics/pharmacodynamics, immunogenicity, and efficacy. Biomarkers were assessed in exploratory analysis.

Results:
No dose-limiting toxicities were observed in the monotherapy (N = 30) or combination (N = 28) dose escalation. LY3321367 treatment-related adverse events (≥2 patients) included pruritus, rash, fatigue, anorexia, and infusion-related reactions. Dose-proportional increase in LY3321367 concentrations was not affected by either LY300054 or antidrug antibodies (observed in 50%–70% of patients). Pharmacokinetic/pharmacodynamic modeling indicated 100% target engagement at doses ≥600 mg. LY3321367 RP2D was 1,200 mg biweekly for four doses followed by 600 mg every 2 weeks thereafter. In the non–small cell lung cancer monotherapy expansion cohort, outcomes varied by prior anti-PD-1 therapy response status: anti-PD-1/L1 refractory patients [N = 23, objective response rate (ORR) 0%, disease control rate (DCR) 35%, progression-free survival (PFS) 1.9 months] versus anti-PD-1/L1 responders (N = 14, ORR 7%, DCR 50%, PFS 7.3 months). In combination expansion cohorts (N = 91), ORR and DCR were 4% and 42%; CD8 infiltration in paired biopsies increased in approximately half these patients.

Conclusions:
LY3321367 exhibited acceptable safety profile with favorable pharmacokinetics/pharmacodynamics but only modest antitumor activity. The therapeutic relevance of TIM-3 blockade requires further investigation.
Preclinical Evaluation of Gilteritinib on NPM1-ALK–Driven Anaplastic Large Cell Lymphoma Cells
Authors: Kuravi Sudhakiranmayi , Cheng Janice , Fangman Gabrielle , Polireddy Kishore , McCormick Sophia , Lin Tara L. , Singh Anurag K. , Abhyankar Sunil , Ganguly Siddhartha , Welch Danny R. , Jensen Roy A. , McGuirk Joseph P. , Balusu Ramesh 
Published: January 2021

Abstract

Anaplastic large cell lymphoma (ALCL) is an aggressive type of non-Hodgkin lymphoma. More than three-fourths of anaplastic lymphoma kinase (ALK)-positive ALCL cases express the nucleophosmin 1 (NPM1)-ALK fusion gene as a result of t(2;5) chromosomal translocation. The homodimerization of NPM1-ALK fusion protein mediates constitutive activation of the chimeric tyrosine kinase activity and downstream signaling pathways responsible for lymphoma cell proliferation and survival. Gilteritinib is a tyrosine kinase inhibitor recently approved by the FDA for the treatment of FMS-like tyrosine kinase mutation–positive acute myeloid leukemia. In this study, we demonstrate for the first time gilteritinib-mediated growth inhibitory effects on NPM1-ALK–driven ALCL cells. We utilized a total of five ALCL model cell lines, including both human and murine. Gilteritinib treatment inhibits NPM1-ALK fusion kinase phosphorylation and downstream signaling, resulting in induced apoptosis. Gilteritinib-mediated apoptosis was associated with caspase 3/9, PARP cleavage, the increased expression of proapoptotic protein BAD, and decreased expression of antiapoptotic proteins, survivin and MCL-1. We also found downregulation of fusion kinase activity resulted in decreased c-Myc protein levels. Furthermore, cell-cycle analysis indicated gilteritinib induced G0–G1-phase cell-cycle arrest and reduced CD30 expression. In summary, our preclinical studies explored the novel therapeutic potential of gilteritinib in the treatment of ALCL cells expressing NPM1-ALK and potentially in other ALK or ALK fusion–driven hematologic or solid malignancies.

Implications:
Our preclinical results explore the use of gilteritinib for the treatment of NPM1-ALK–driven ALCL cells and pave a path for developing future clinical trials.
The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis
Authors: Park Jae Jun , Kim Byung Chang , Hong Sung Pil , Seo Yoojeong , Lee Hye Sun , Park Young Sook , Na Soo-Young , Park Sung Chul , Park Jongha , Kim Jae Hak , Moon Chang Mo , Huh Kyu Chan , Park Soo Jung , Cheon Jae Hee , Kim Won Ho , Kim Tae Il 
Published: January 2021

Abstract

Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the development of numerous colorectal adenomas in young adults. Metformin, an oral diabetic drug, has been shown to have antineoplastic effects and a favorable safety profile. We performed a randomized, double-blind, controlled trial to evaluate the efficacy of metformin on the regression of colorectal and duodenal adenoma in patients with FAP. Thirty-four FAP patients were randomly assigned in a 1:2:2 ratio to receive placebo, 500 mg metformin, or 1,500 mg metformin per day orally for 7 months. The number and size of polyps and the global polyp burden were evaluated before and after the intervention. This study was terminated early based on the results of the interim analysis. No significant differences were determined in the percentage change of colorectal and duodenal polyp number over the course of treatment among the three treatment arms (P = 0.627 and P = 1.000, respectively). We found no significant differences in the percentage change of colorectal or duodenal polyp size among the three groups (P = 0.214 and P = 0.803, respectively). The overall polyp burdens of the colorectum and duodenum were not significantly changed by metformin treatment at either dosage. Colon polyps removed from the metformin-treated patients showed significantly lower mTOR signal (p-S6) expression than those from patients in the placebo arm. In conclusion, 7 months of treatment with 500 mg or 1,500 mg metformin did not reduce the mean number or size of polyps in the colorectum or duodenum in FAP patients (ClinicalTrials.gov ID: NCT01725490).

Prevention Relevance:
A 7-month metformin treatment (500 mg or 1,500 mg) did not reduce the number or size of polyps in the colorectum or duodenum of FAP patients as compared to placebo. These results do not support the use of metformin to promote regression of intestinal adenomas in FAP patients.
Chromatin Accessibility of Human Mitral Valves and Functional Assessment of MVP Risk Loci
Authors: Kyryachenko Sergiy , Georges Adrien , Yu Mengyao , Barrandou Takiy , Guo Lilong , Bruneval Patrick , Rubio Tony , Gronwald Judith , Baraki Hassina , Kutschka Ingo , Aras Kedar K. , Efimov Igor R. , Norris Russel A. , Voigt Niels , Bouatia-Naji Nabila 
Published: January 2021

Rationale:
Mitral valve prolapse (MVP) is a common valvopathy that leads to mitral insufficiency, heart failure, and sudden death. Functional genomic studies in mitral valves are needed to better characterize MVP-associated variants and target genes.

Objective:
To establish the chromatin accessibility profiles and assess functionality of variants and narrow down target genes at MVP loci.

Methods and Results:

We mapped the open chromatin regions in nuclei from 11 human pathogenic and 7 nonpathogenic mitral valves by an assay for transposase-accessible chromatin with high-throughput sequencing. Open chromatin peaks were globally similar between pathogenic and nonpathogenic valves. Compared with the heart tissue and cardiac fibroblasts, we found that MV-specific assay for transposase-accessible chromatin with high-throughput sequencing peaks are enriched near genes involved in extracellular matrix organization, chondrocyte differentiation, and connective tissue development. One of the most enriched motifs in MV-specific open chromatin peaks was for the nuclear factor of activated T cells family of TFs (transcription factors) involved in valve endocardial and interstitial cell formation. We also found that MVP-associated variants were significantly enriched (
P
<0.05) in mitral valve open chromatin peaks. Integration of the assay for transposase-accessible chromatin with high-throughput sequencing data with risk loci, extensive functional annotation, and gene reporter assay suggest plausible causal variants for rs2641440 at the
SMG6/SRR
locus and rs6723013 at the
IGFBP2/IGFBP5/TNS1
locus. CRISPR-Cas9 deletion of the sequence including rs6723013 in human fibroblasts correlated with increased expression only for
TNS1
. Circular chromatin conformation capture followed by high-throughput sequencing experiments provided evidence for several target genes, including
SRR
,
HIC1
, and
DPH1
at the
SMG6/SRR
locus and further supported
TNS1
as the most likely target gene on chromosome 2.

Conclusions:
Here, we describe unprecedented genome-wide open chromatin profiles from human pathogenic and nonpathogenic MVs and report specific gene regulation profiles, compared with the heart. We also report in vitro functional evidence for potential causal variants and target genes at MVP risk loci involving established and new biological mechanisms.

Graphic Abstract:

A
graphic abstract
is available for this article.
Shifting Priorities: Are Attitudes Changing at the International Criminal Court about Trials in absentia?
Authors: Wheeler Caleb H. 
Published: January 2021

Abstract
A recent decision by the International Criminal Court’s Appeals Chamber in the Gbagbo and Blé Goudé case raised the possibility of a shift away from the long-standing practice of only holding trial in the presence of the accused. The final paragraphs of the 28 May 2020 decision asserts that any future trial proceedings in the Gbagbo et al. case could be held in the absence of the defendants should Mr Gbagbo and Mr Blé Goudé be released from custody and then later fail to appear for trial. This article examines the Appeals Chamber’s decision in light of the Court’s Statute, existing jurisprudence at the icc and within the larger context of international criminal law. It concludes that the Appeals Chamber’s decision fails to properly understand the right to be present at trial as it exists in the Rome Statute nor does it comply with any identified general principle of law.
Climatology of Borneo Vortices in the HadGEM3-GC3.1 General Circulation Model
Authors: Liang Ju , Catto Jennifer L. , Hawcroft Matthew , Hodges Kevin I. , Tan Mou Leong , Haywood James M. 
Published: January 2021

AbstractBorneo vortices (BVs) are intense precipitating winter storms that develop over the equatorial South China Sea and strongly affect the weather and climate over the western Maritime Continent because of their association with deep convection and heavy rainfall. In this study, the ability of the Hadley Centre Global Environment Model 3–Global Coupled, version 3.1 (HadGEM3-GC3.1), global climate model to simulate the climatology of BVs at different horizontal resolutions is examined using an objective feature-tracking algorithm. The HadGEM3-GC3.1 at the N512 (25 km) horizontal resolution simulates BVs with well-represented characteristics, including their frequency, spatial distribution, and lower-tropospheric structures when compared with BVs identified in a climate reanalysis, whereas the BVs in the N96 (~135 km) and N216 (~65 km) simulations are much weaker and less frequent. Also, the N512 simulation better captures the contribution of BVs to the winter precipitation in Borneo and the Malay Peninsula when compared with precipitation from a reanalysis data and from observations, whereas the N96 and N216 simulations underestimate this contribution because of the overly weak low-level convergence of the simulated BVs. The N512 simulation also exhibits an improved ability to reproduce the modulation of BV activity by the occurrence of northeasterly cold surges and active phases of the Madden–Julian oscillation in the region, including increased BV track densities, intensities, and lifetimes. A sufficiently high model resolution is thus found to be important to realistically simulate the present-climate precipitation extremes associated with BVs and to study their possible changes in a warmer climate.