bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing door-to-reperfusion time in acute stroke endovascular therapy using magnetic resonance imaging as a screening modality
Authors: Sakamoto Yuki , Suzuki Kentaro , Abe Arata , Aoki Junya , Kanamaru Takuya , Takayama Yohei , Katano Takehiro , Kutsuna Akihito , Suda Satoshi , Nishiyama Yasuhiro , Nito Chikako , Kimura Kazumi 
Published: February 2020

BackgroundThe feasibility of performing MRI first for patients with suspected hyperacute stroke in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-reperfusion time (DRT) in endovascular treatment (EVT) were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and to examine the effects of a quality improvement (QI) process for reducing DRT using MRI.MethodsFrom January 2013 to December 2018, consecutive patients with acute stroke who came to hospital directly and were treated with emergent EVT were prospectively enrolled into the present study. In principle, MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DRT was adopted during this period. Time metrics for EVT were compared between specific time periods.ResultsA total of 180 patients (71 women; median age 76 years (range 69–64); National Institutes of Health Stroke Scale score 17 (range 10–23)) were included in the present study. More patients in the late phase were managed with the MRI-first policy (p<0.001). DRT (199 min in Phase 1, 135 min in Phase 2, 129 min in Phase 3, and 121 min in Phase 4, p<0.001) was significantly reduced across the phases. The percentage of patients with DRT <120 min increased significantly across time periods (p<0.001). Symptomatic intracerebral hemorrhage did not increase across phases (p=0.575).ConclusionAn MRI-first policy was feasible, and DRT decreased considerably with a step-by-step QI process. This process may be applicable to other hospitals.
Epidemiological study of dogs with diabetes mellitus attending primary care veterinary clinics in Australia
Authors: Yoon Samuel , Fleeman Linda M , Wilson Bethany J , Mansfield Caroline S , McGreevy Paul 
Published: February 2020

BackgroundThe objectives of this study were to establish the prevalence, risk factors and comorbidities/sequelae for diabetes mellitus (DM) in Australian dogs presented to first‐opinion veterinary practices.MethodsElectronic patient records of dogs (n=134,329) attending 152 veterinary clinics during 2017 were sourced through VetCompass Australia. They included 418 dogs with DM; a prevalence of 0.36 per cent (95 per cent CI 0.33 per cent to 0.39 per cent) in Australian dogs attending these veterinary clinics. By comparing with the reference group of rarer breeds and unidentified crossbreeds, multivariable modelling was used to reveal breeds (and their crosses) with significantly higher odds of having DM.ResultsThe results revealed that breeds (and their crosses) with significantly higher odds of having DM were Australian terriers (ORs=7.93 (95 per cent CI 2.83 to 22.27)), Siberian huskies (OR=6.24 (95 per cent CI 2.51 to 15.54)), English springer spaniels (OR=5.37 (95 per cent CI 1.48 to 19.53)), West Highland white terriers (OR=4.85 (95 per cent CI 2.55 to 9.25)), miniature schnauzers (OR=3.47 (95 per cent CI 1.16 to 10.35)), all types of poodles (OR=3.41 (95 per cent CI 2.07 to 5.61)), bichon frises (OR=3.41 (95 per cent CI 1.65 to 7.01)), schnauzers (OR=3.18 (95 per cent CI 1.42 to 7.11)) and cavalier King Charles spaniels (CKCS; OR=1.84 (95 per cent CI 1.08 to 3.13)). Breeds with lower risk were German shepherd dogs (OR=0.11 (95 per cent CI 0.01 to 0.84)), golden retrievers (OR=0.09 (95 per cent CI 0.01 to 0.68)) and boxers (no cases identified). Fisher’s exact tests showed that labradoodles were diagnosed significantly more often than purebred Labradors (P=0.04) and did not differ significantly from poodles (P=0.81). Cavoodles did not differ significantly from either CKCS (p~1.00) or poodles (P=0.12). Spoodles were significantly less diagnosed than poodles (P=0.003) but did not differ from cocker spaniels (P=0.66). Desexed male dogs had a higher odds of DM than entire male (OR=0.62 (95 per cent CI 0.39 to 0.98)) and desexed female dogs (OR=0.76 (95 per cent CI 0.61 to 0.96)). Comorbidities/sequelae associated with canine DM included suspected pancreatitis (OR 10.58 (95 per cent CI 5.17 to 22.78)), cataracts (OR 9.80 (95 per cent CI 5.65 to 17.35)), hyperadrenocorticism (OR 6.21 (95 per cent CI 3.29 to 11.88)), urinary tract infection (OR 5.09 (95 per cent CI 1.97 to 13.41)) and hypothyroidism (OR 4.10 (95 per cent CI 1.08 to 15.58)).ConclusionsBreeds at most risk included Australian terriers and Siberian huskies as previously reported, as well as, for the first time, English springer spaniels. In contrast to other populations where there is female predisposition for DM, desexed male dogs in Australia were at increased risk for DM compared with both entire males and desexed females. This predisposition for desexed males to develop DM warrants further investigation.
Prednisolone therapy for chronic hepatitis in English springer spaniels: a prospective study of 12 cases
Authors: Bayton William , Watson Penny J , Bexfield Nicholas H 
Published: February 2020

BackgroundEnglish springer spaniels (ESS) show an increased risk of chronic hepatitis (CH). In a previous study of 68 ESS with CH, in which only one dog received corticosteroids, a median survival time of 189 days was noted. Some ESS with CH appear to improve with prednisolone treatment; therefore, we aimed to investigate the response to prednisolone in this breed.ParticipantsESS with histologically confirmed idiopathic CH were treated with prednisolone 1–2 mg/kg/day. Nine female and three male ESS were enrolled (median age at diagnosis of five years). Patients were monitored clinically and had biochemistry samples taken to assess markers of hepatocellular damage and function.ResultsThe mean starting dose of prednisolone was 1.1 mg/kg/day. All symptomatic patients showed an initial clinical improvement. Two cases were euthanased while receiving prednisolone. The median time since diagnosis is 1715 days (range: 672–2105 days) and the remaining patients are clinically well, with seven patients still receiving a mean dose of 0.4 mg/kg prednisolone every other day. Statistical analysis demonstrated significant (P<0.05) reductions in serum alkaline phosphatase, alanine aminotransferase and bilirubin following 2–4 weeks of prednisolone treatment.ConclusionThis study demonstrates improved clinical and biochemical parameters when some ESS with CH are managed with prednisolone and standard supportive treatments.
Phase-coherent caloritronics with ordinary and topological Josephson junctions
Authors: Hwang Sun-Yong , Sothmann Björn 
Published: February 2020

Abstract
We provide a brief and comprehensive overview over recent developments in the field of phase-coherent caloritronics in ordinary and topological Josephson junctions. We start from the simple case of a short, one-dimensional superconductor-normal metal-superconductor (S-N-S) Josephson junction and derive the phase-dependent thermal conductance within the Bogoliubov-de Gennes formalism. Then, we review the key experimental breakthroughs that have triggered the recent growing interest into phase-coherent heat transport. They include the realization of thermal interferometers, diffractors, modulators and routers based on superconducting tunnel junctions. Finally, we discuss very recent theoretical findings based on superconductor-topological insulator-superconductor (S-TI-S) Josephson junctions that show interesting heat transport properties due to the interplay between topological band structures and superconductivity.
Skill acquisition is enhanced by reducing trial-to-trial repetition
Authors: Vleugels Lore W. E. , Swinnen Stephan P. , Hardwick Robert M. 
Published: February 2020

Developing approaches to improve motor skill learning is of considerable interest across multiple disciplines. Previous research has typically shown that repeating the same action on consecutive trials enhances short-term performance but has detrimental effects on longer term skill acquisition. However, most prior research has contrasted the effects of repetition only at the block level; in the current study we examined the effects of repeating individual trials embedded in a larger randomized block, a feature that is often overlooked when random trial orders are generated in learning tasks. With 4 days of practice, a “Minimal Repeats” group, who rarely experienced repeating stimuli on consecutive trials during training, improved to a greater extent than a “Frequent Repeats” group, who were frequently presented with repeating stimuli on consecutive trials during training. Our results extend the previous finding of the beneficial effects of random compared with blocked practice on performance, showing that reduced trial-to-trial repetition during training is favorable with regard to skill learning. This research highlights that limiting the number of repeats on consecutive trials is a simple behavioral manipulation that can enhance the process of skill learning. Data/analysis code and Supplemental Material are available at https://osf.io/p3278/ . NEW & NOTEWORTHY Numerous studies have shown that performing different subtasks across consecutive blocks of trials enhances learning. We examined whether the same effect would occur on a trial-to-trial level. Our Minimal Repeats group, who primarily responded to different stimuli on consecutive trials, learned more than our Frequent Repeats group, who frequently responded to the same stimulus on consecutive trials. This shows that minimizing trial-to-trial repetition is a simple and easily applicable manipulation that can enhance learning.
Pancreatic Cancer Risk in Relation to Lifetime Smoking Patterns, Tobacco Type, and Dose–Response Relationships
Authors: Molina-Montes Esther , Van Hoogstraten Lisa , Gomez-Rubio Paulina , Löhr Matthias , Sharp Linda , Molero Xavier , Márquez Mirari , Michalski Christoph W. , Farré Antoni , Perea José , O'Rorke Michael , Greenhalf William , Ilzarbe Lucas , Tardon Adonina , Gress Thomas M. , Barberà Victor M. , Crnogorac-Jurcevic Tatjana , Muñoz-Bellvis Luis , Domínguez-Muñoz Enrique , Balsells Joaquim , Costello Eithne , Iglesias Mar , Kleeff Jorg , Kong Bo , Mora Josefina , O'Driscoll Damian , Poves Ignasi , Scarpa Aldo , Yu Jingru , Ye Weimin , Hidalgo Manuel , Carrato Alfredo , Lawlor Rita , Real Francisco X. , Malats Nuria 
Published: February 2020

AbstractBackground:Despite smoking being a well-established risk factor for pancreatic cancer, there is a need to further characterize pancreatic cancer risk according to lifespan smoking patterns and other smoking features, such as tobacco type. Our aim was to deeply investigate them within a large European case–control study.Methods:Tobacco smoking habits and other relevant information were obtained from 2,009 cases and 1,532 controls recruited in the PanGenEU study using standardized tools. Multivariate logistic regression analysis was performed to evaluate pancreatic cancer risk by smoking characteristics and interactions with other pancreatic cancer risk factors. Fractional polynomials and restricted cubic splines were used to test for nonlinearity of the dose–response relationships and to analyze their shape.Results:Relative to never-smokers, current smokers [OR = 1.72; 95% confidence interval (95% CI), 1.39–2.12], those inhaling into the throat (OR = 1.48; 95% CI, 1.11–1.99) or chest (OR = 1.33; 95% CI, 1.12–1.58), and those using nonfiltered cigarettes (OR = 1.69; 95% CI, 1.10–2.61), were all at an increased pancreatic cancer risk. Pancreatic cancer risk was highest in current black tobacco smokers (OR = 2.09; 95% CI, 1.31–3.41), followed by blond tobacco smokers (OR = 1.43; 95% CI, 1.01–2.04). Childhood exposure to tobacco smoke relative to parental smoking was also associated with increased pancreatic cancer risk (OR = 1.24; 95% CI, 1.03–1.49). Dose–response relationships for smoking duration, intensity, cumulative dose, and smoking cessation were nonlinear and showed different shapes by tobacco type. Effect modification by family history of pancreatic cancer and diabetes was likely.Conclusions:This study reveals differences in pancreatic cancer risk by tobacco type and other habit characteristics, as well as nonlinear risk associations.Impact:This characterization of smoking-related pancreatic cancer risk profiles may help in defining pancreatic cancer high-risk populations.
Total Antioxidant Capacity and Pancreatic Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Zhong Guo-Chao , Pu Jian-Yuan , Wu Yi-Lin , Yi Zhu-Jun , Wan Lun , Wang Kang , Hao Fa-Bao , Zhao Yong , Gong Jian-Ping 
Published: February 2020

AbstractBackground:Total antioxidant capacity (TAC) reflects an individual's overall antioxidant intake. We sought to clarify whether higher TAC is associated with lower risks of pancreatic cancer incidence and mortality in the U.S. general population.Methods:A total of 96,018 American adults were identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A ferric-reducing ability of plasma score was used to reflect an individual's TAC intake from diet and/or supplements. Cox regression was used to calculate hazard ratios (HR) for pancreatic cancer incidence, and competing risk regression was used to calculate subdistribution HRs for pancreatic cancer mortality. Restricted cubic spline regression was used to test nonlinearity.Results:A total of 393 pancreatic cancer cases and 353 pancreatic cancer–related deaths were documented. Total (diet + supplements) TAC was found to be inversely associated with pancreatic cancer incidence (HR quartile 4 vs. quartile 1 = 0.53; 95% confidence interval, 0.39–0.72; Ptrend = 0.0002) and mortality (subdistribution HR quartile 4 vs. quartile 1 = 0.52; 95% confidence interval 0.38–0.72; Ptrend = 0.0003) in a nonlinear dose–response manner (all Pnonlinearity &lt; 0.01). Similar results were observed for dietary TAC. No association of supplemental TAC with pancreatic cancer incidence and mortality was found.Conclusions:In the U.S. general population, dietary but not supplemental TAC level is inversely associated with risks of pancreatic cancer incidence and mortality in a nonlinear dose–response pattern.Impact:This is the first prospective study indicating that a diet rich in antioxidants may be beneficial in decreasing pancreatic cancer incidence and mortality.
Nucleostemin Modulates Outcomes of Hepatocellular Carcinoma via a Tumor Adaptive Mechanism to Genomic Stress
Authors: Wang Junying , McGrail Daniel J. , Bhupal Parnit K. , Zhang Wen , Lin Kuan-Yu , Ku Yi-Hsuan , Lin Tao , Wu Hongfu , Tsai Kyle C. , Li Kaiyi , Peng Cheng-Yuan , Finegold Milton J. , Lin Shiaw-Yih , Tsai Robert Y.L. 
Published: February 2020

Abstract

Hepatocellular carcinomas (HCC) are adapted to survive extreme genomic stress conditions imposed by hyperactive DNA replication and genotoxic drug treatment. The underlying mechanisms remain unclear, but may involve intensified DNA damage response/repair programs. Here, we investigate a new role of nucleostemin (NS) in allowing HCC to survive its own malignancy, as NS was previously shown to promote liver regeneration via a damage repair mechanism. We first established that a higher NS transcript level correlates with high-HCC grades and poor prognostic signatures, and is an independent predictor of shorter overall and progression-free survival specifically for HCC and kidney cancer but not for others. Immunostaining confirmed that NS is most abundantly expressed in high-grade and metastatic HCCs. Genome-wide analyses revealed that NS is coenriched with MYC target and homologous recombination (HR) repair genes in human HCC samples and functionally intersects with those involved in replication stress response and HR repair in yeasts. In support, NS-high HCCs are more reliant on the replicative/oxidative stress response pathways, whereas NS-low HCCs depend more on the mTOR pathway. Perturbation studies showed NS function in protecting human HCC cells from replication- and drug-induced DNA damage. Notably, NS depletion in HCC cells increases the amounts of physical DNA damage and cytosolic double-stranded DNA, leading to a reactive increase of cytokines and PD-L1. This study shows that NS provides an essential mechanism for HCC to adapt to high genomic stress for oncogenic maintenance and propagation. NS deficiency sensitizes HCC cells to chemotherapy but also triggers tumor immune responses.

Implications:
HCC employs a novel, nucleostemin (NS)-mediated-mediated adaptive mechanism to survive high genomic stress conditions, a deficiency of which sensitizes HCC cells to chemotherapy but also triggers tumor immune responses.
Morphofunctional Effects of C5 Convertase Blockade in Immune Complex-Mediated Membranoproliferative Glomerulonephritis: Report of Two Cases with Evidence of Terminal Complement Activation
Authors: Carrara Camillo , Podestà Manuel Alfredo , Abbate Mauro , Rizzo Paola , Piras Rossella , Alberti Marta , Daina Erica , Ruggenenti Piero , Remuzzi Giuseppe ,   on behalf of the EAGLE Study Group
Published: February 2020

A membranoproliferative pattern of glomerular injury is frequently observed in patients with complement-mediated disorders, such as C3 glomerulopathies (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). The outcomes of C3G and ­IC-MPGN are poor, independently of immunosuppressive therapy. However, two 48-week treatment periods with the anti-C5 monoclonal antibody eculizumab, divided by a ­12-week washout period, achieved remission of proteinuria and stabilization/improvement of the glomerular filtration rate (GFR), measured through iohexol plasma clearance, in 3 of 10 patients with biopsy-proven MPGN, nephrotic syndrome and terminal complement complex sC5b-9 plasma levels &#x3e;1,000 mg/mL, at inclusion. Baseline and end-of-study kidney biopsies were available for 2 patients with IC-MPGN, and their baseline characteristics were similar. However, in 1 patient proteinuria and GFR did not improve during the study, whereas in the other proteinuria decreased from 4.84 to 2.12 g/24-h and GFR increased from 91.5 to 142.7 mL/min/1.73 m<sup>2</sup>. Glomerular inflammation improved and median (interquartile range) glomerular staining for C5b-9 decreased in both cases: from 23.6 to 18.2% (<i>p</i> = 0.021) in the patient who achieved remission and from 15.8 to 10.7% (<i>p</i> = 0.019) in the patient with persistent proteinuria. Chronic glomerular lesions progressed and C3 glomerular staining and electron-dense deposits did not change appreciably in either case. However, in the patient who achieved remission, ultrastructural evaluation revealed features of glomerular microangiopathy at inclusion, which fully recovered posttreatment. Podocyte foot process effacement was observed in both patients at inclusion, but recovered only in the patient with microangiopathy. Thus, in 2 patients with ­IC-MPGN, chronic glomerular changes progressed despite eculizumab-induced amelioration of glomerular inflammation and inhibition of sC5b-9 deposition, and independently of treatment effects on proteinuria and podocytes. The finding that the regression of microangiopathic changes was associated with improved clinical outcomes suggests that C5 blockade might have a therapeutic role in patients with IC-MPGN displaying microangiopathic endothelial injury.
Melbourne Mobile Stroke Unit and Reperfusion Therapy
Authors: Zhao Henry , Coote Skye , Easton Damien , Langenberg Francesca , Stephenson Michael , Smith Karen , Bernard Stephen , Cadilhac Dominique A. , Kim Joosup , Bladin Christopher F. , Churilov Leonid , Crompton Douglas E. , Dewey Helen M. , Sanders Lauren M. , Wijeratne Tissa , Cloud Geoffrey , Brooks Duncan M. , Asadi Hamed , Thijs Vincent , Chandra Ronil V. , Ma Henry , Desmond Patricia M. , Dowling Richard J. , Mitchell Peter J. , Yassi Nawaf , Yan Bernard , Campbell Bruce C.V. , Parsons Mark W. , Donnan Geoffrey A. , Davis Stephen M. 
Published: February 2020

Background and Purpose—
Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU.

Methods—
Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates.

Results—

In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was administered to 100 patients (mean age, 73.8 years; 62% men). The median time savings per MSU patient, compared with the control cohort, was 26 minutes (
P
<0.001) for dispatch to hospital arrival and 15 minutes (
P
<0.001) for hospital arrival to thrombolysis. The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes (95% CI, 36.0–49.0). In the same period, 41 MSU patients received EVT (mean age, 76 years; 61% men) with median dispatch-to-treatment time saving of 51 minutes ([95% CI, 30.1–71.9],
P
<0.001). This included a median time saving of 17 minutes ([95% CI, 7.6–26.4],
P
=0.001) for EVT hospital arrival to arterial puncture for MSU patients. Estimated median disability-adjusted life years saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

Conclusions—
The Melbourne MSU substantially reduced time to reperfusion therapies, with the greatest estimated disability avoidance driven by the more powerful impact of earlier EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.