bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of glucagon‐like peptide‐1/glucagon receptor co‐agonist JNJ‐64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose‐ranging study
Authors: Alba Maria , Yee Jaqueline , Frustaci Mary Ellen , Samtani Mahesh N. , Fleck Penny 
Published: January 2021

SummaryIndividuals with obesity have a heightened risk of developing serious comorbidities, and pharmacological treatments for people with obesity are limited. This phase 2 study assessed the safety and efficacy of JNJ‐64565111, a dual agonist of glucagon‐like peptide‐1 and glucagon receptors, in individuals with class II/III obesity without type 2 diabetes. In this randomized, double‐blind, placebo‐controlled and open‐label active‐controlled, parallel‐group, multicentre study, participants aged 18 to 70 years with a body mass index of 35 to 50 kg/m2 and stable weight were randomly assigned in a 1:1:2:2:2 ratio to blinded treatment with placebo; JNJ‐64565111 (5.0, 7.4 or 10.0 mg, each with no dose escalation), or open‐label liraglutide 3.0 mg. The primary efficacy endpoint was percent change from baseline in body weight at week 26. Four‐hundred seventy four participants were randomized and 343 (72.4%) completed treatment. At week 26, placebo‐subtracted body weight changes (adjusted for multiplicity) were −6.8%, −8.1% and −10.0% for the JNJ‐64565111 5.0 mg, 7.4 mg and 10.0 mg groups, respectively, and −5.8% for the liraglutide group. Incidence of treatment‐emergent adverse events, especially nausea and vomiting, was higher in each JNJ‐64565111 treatment group compared to placebo and liraglutide. JNJ‐64565111 significantly reduced body weight in a dose‐dependent manner vs placebo but was associated with greater incidence of treatment‐emergent adverse events.
Efficacy and safety of glucagon‐like peptide‐1/glucagon receptor co‐agonist JNJ‐64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose‐ranging study
Authors: Di Prospero Nicholas A. , Yee Jaqueline , Frustaci Mary E. , Samtani Mahesh N. , Alba Maria , Fleck Penny 
Published: January 2021

SummaryWeight loss has been shown to improve metabolic parameters and cardiovascular risk in people with type 2 diabetes mellitus (T2DM). This phase 2 study evaluated the safety and efficacy of JNJ‐64565111, a dual agonist of GLP‐1 and glucagon receptors, in individuals with T2DM and class II/III obesity. In this randomized, double‐blind study, participants with T2DM (HbA1c 6.5%‐9.5%), body mass index of 35 to 50 kg/m2 and stable weight were randomly assigned (1:1:1:1) to placebo or JNJ‐64565111 (5.0 mg, 7.4 mg or 10.0 mg). The primary endpoint was percent change from baseline in body weight at week 12. Of 195 dosed participants, 144 (73.8%) completed treatment. At week 12, placebo‐subtracted body weight changes were −4.6%, −5.9% and −7.2% with JNJ‐64565111 5.0 mg, 7.4 mg and 10.0 mg, respectively. All JNJ‐64565111 doses were associated with no change in HbA1c and slight numerical elevation of fasting insulin. Numerical increases in fasting plasma glucose were observed with JNJ‐64565111 5.0 mg and 7.4 mg. Incidence of treatment‐emergent adverse events, especially nausea and vomiting, was higher with JNJ‐64565111 vs placebo. Overall, JNJ‐64565111 significantly reduced body weight in a dose‐dependent manner vs placebo but was associated with greater incidence of treatment‐emergent adverse events, no HbA1c reductions, and increased fasting plasma glucose and fasting insulin.
Impact of a history of metastases or synchronous metastases on survival in patients with locally recurrent rectal cancer
Authors: Voogt E. L. K. , van Zoggel D. M. G. I. , Kusters M. , Nieuwenhuijzen G. A. P. , Cnossen J. S. , Creemers G. J. , van Lijnschoten G. , Nederend J. , Roef M. J. , Burger J. W. A. , Rutten H. J. T. 
Published: January 2021

AbstractAimPatients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases.MethodAll consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis.ResultsOf the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3‐year metastasis‐free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98–2.11).ConclusionLRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis‐free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.
Season‐long characterization of high‐cannabinoid hemp (Cannabis sativa L.) reveals variation in cannabinoid accumulation, flowering time, and disease resistance
Authors: Stack George M. , Toth Jacob A. , Carlson Craig H. , Cala Ali R. , Marrero‐González Mariana I. , Wilk Rebecca L. , Gentner Deanna R. , Crawford Jamie L. , Philippe Glenn , Rose Jocelyn K. C. , Viands Donald R. , Smart Christine D. , Smart Lawrence B. 
Published: January 2021

AbstractGiven the dramatic rise in high‐cannabinoid hemp (Cannabis sativa L.) production in the last decade, there is an increasingly urgent need to characterize available germplasm and develop knowledge to accelerate the breeding of uniform and stable cultivars. Despite persistent cultivation of hemp cultivars for grain and or fiber around the world, the diversity and genetic underpinning of key traits for breeding and cultivation are poorly understood. For 30 high‐cannabidiol hemp cultivars replicated on two field sites, we sought to evaluate yield, agronomic performance, and disease resistance while also conducting a detailed study of cannabinoid accumulation over the course of floral maturation. We observed significant variation in both within and among cultivars. During the growing season, the plants clustered into five groups by growth rate and varied in flowering time from photoperiod insensitive to photoperiod sensitive with very short critical photoperiods. Based on the observed ratio of total potential cannabidiol (CBD) to total potential tetrahydrocannabinol (THC), there was segregation for cannabinoid chemotype in some seeded cultivar populations. Analysis of cannabichromene (CBC) production revealed that some cultivars had a discretely lower CBD:CBC ratio than the others. There was a continuous range of powdery mildew severity by cultivar, with one that had little to no observed powdery mildew suggesting it might have genetic resistance. Biomass production at harvest was strongly influenced by location and cultivar, and there was variation by cultivar in the relative cannabinoid production in shoot tip samples compared with whole plant samples. While our results provide preliminary guidance regarding relative performance of current cultivars, our analyses indicate a need for additional hemp breeding to provide stable, uniform, and legally compliant cultivars with improved disease resistance and flowering times optimized for the latitudes of different growing locations.
Nanoscale Chemical Imaging by Photo‐Induced Force Microscopy: Technical Aspects and Application to the Geosciences
Authors: Otter Laura M. , Förster Michael W. , Belousova Elena , O’Reilly Padraic , Nowak Derek , Park Sung , Clark Simon , Foley Stephen F. , Jacob Dorrit E. 
Published: January 2021

Photo‐induced force microscopy (PiFM) is a new‐frontier technique that combines the advantages of atomic force microscopy with infrared spectroscopy and allows for the simultaneous acquisition of 3D topographic data with molecular chemical information at high spatial (~ 5 nm) and spectral (~ 1 cm−1) resolution at the nanoscale. This non‐destructive technique is time efficient as it requires only conventional mirror‐polishing and has fast mapping rates on the order of a few minutes that allow the study of dynamic processes via time series. Here, we review the method’s historical development, working principle, data acquisition, and evaluation, and provide a comparison with traditional geochemical methods. We review PiFM studies in the areas of materials science, chemistry and biology. In addition, we provide the first applications for geochemical samples including the visualization of faint growth zonation in zircons, the identification of fluid speciation in high‐pressure experimental samples, and of nanoscale organic phases in biominerals. We demonstrate that PiFM analysis is a time‐ and cost‐efficient technique combining high‐resolution surface imaging with molecular chemical information at the nanoscale and, thus, complements and expands traditional geochemical methods.
Video‐enhanced or textual rubrics: Does the Viewbrics' formative assessment methodology support the mastery of complex (21st century) skills?
Authors: Ackermans Kevin , Rusman Ellen , Nadolski Rob , Specht Marcus , Brand‐Gruwel Saskia 
Published: January 2021

AbstractLearners in the process of developing complex skills need a rich mental model of what such skills entail. Textual analytics rubrics (TR) are a widely used instrument to support formative assessment of complex skills, supporting feedback, reflection, and thus mental model development of complex skills. However, the textual nature of a rubric limits the possibility to deliver contextual and dynamic (time‐and behaviour‐oriented) information. In the Viewbrics online tool, we developed a version supporting the delivery of contextual and dynamic information by adding video‐modelling examples with embedded self‐explanation prompts to textual analytics rubrics. We called this combination as video‐enhanced rubrics (VERs). Our current study investigates whether the Viewbrics online tool supports complex skills development and whether either textual‐ or video‐enhanced rubrics best support complex skills' mastery. The study was a three‐group (VERS n = 49, TR n = 54, control n = 50) within‐subjects design. Learners' performance of complex skills was measured through expert, peer, and self‐assessment using the Viewbrics online tool. A multilevel regression analysis shows learners in the TR and VERS conditions consistently outperforming the control condition to varying degrees across skills. However, no differences have been found between the two experimental conditions. Positive results across different complex skills indicate the Viewbrics online tool can be used to support the development of a wide range of complex skills in secondary education.
Ultralow temperature cryoablation: Safety and efficacy of preclinical atrial and ventricular lesions
Authors: Bourier Felix , Takigawa Masateru , Lam Anna , Vlachos Konstantinos , Ramirez F. Daniel , Martin Claire A. , Frontera Antonio , Kitamura Takeshi , Duchateau Josselin , Pambrun Thomas , Derval Nicolas , Denis Arnaud , Cox Jerry , Cabrita David , Babkin Alexander , Constantin Marion , Jais Pierre , Sacher Frédéric , Dubois Rémi , Bernus Oliver , Haissaguerre Michel , Hocini Mélèze 
Published: January 2021

AbstractBackgroundUltralow temperature cyroablation (ULTC) is designed to create focal, linear, and circumferential lesions. The aim of this study was to assess the safety, efficacy, and durability of atrial and ventricular ULTC lesions in preclinical large animal models.Methods and ResultsThe ULTC system uses nitrogen near its liquid‐vapor critical point to cool 11‐cm ablation catheters. The catheter can be shaped to specific anatomies using pre‐shaped stylets. ULTC was used in 11 swine and four sheep to create atrial (pulmonary vein isolation and linear ablation) and ventricular lesions. Acute and 90‐day success were evaluated by intracardiac mapping and histologic examination. Cryoadherence was observed during all ULTC applications, ensuring catheter stability at target locations. Local electrograms were completely eliminated immediately after the first single‐shot ULTC application in 49 of 53 (92.5%) atrial and in 31 of 32 (96.9%) ventricular applications. Lesion depth as measured on histology preparations was 1.96 ± 0.8 mm in atrial and 5.61 ± 2.2 mm in ventricular lesions. In all animals, voltage maps and histology demonstrated transmural and durable lesions without gaps, surrounded by intact collagen fibers without injury to surrounding tissues. Transient coronary spasm could be provoked with endocardial ULTC in the left ventricle in close proximity to a coronary artery.ConclusionsULTC created effective and efficient atrial and ventricular lesions in vivo without procedural complications in two large animal models. ULTC lesions were transmural, contiguous, and durable over 3 months.
Politicization of Aiding Others: The Impact of Migration on European Public Opinion of Development Aid
Authors: Kiratli Osman Sabri 
Published: January 2021

AbstractThis article provides a longitudinal analysis on the driving forces behind Europeans' positions toward development aid and identifies changes in the dynamics following the migrant flows in 2015. Specifically, it assesses the extent to which policy‐makers' decisions to utilize development policy as a strategic tool to manage migration resonates at the public level. Using multilevel regression models on cross‐sectional survey data acquired from Eurobarometer surveys covering five waves between 2013 and 2018, supplemented by a series of macro‐level covariates both at the country and regional level, I show that voters in countries and regions with higher numbers of migrants are more supportive of foreign aid. The models also verify that support for foreign aid in polities that are the destination for migrants is substantially stronger in surveys conducted after 2015 than before and among voters who are interested in politics.
Efficacy of once‐daily glucagon‐like peptide‐1 receptor agonist lixisenatide as an add‐on treatment to basal insulin in Asian and white adults with type 2 diabetes mellitus: An individual‐level pooled analysis of phase III studies
Authors: Liu Fuqiang , Liu Yuan , Liu Minzhi , Wu Guangyu , Zhang Minlu , Zhang Xia , Cui Nan , Yin Huiqiu , Chen Li 
Published: January 2021

AbstractAims/IntroductionThe prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin.Materials and MethodsAn individual‐level pooled analysis of two multi‐national phase III studies, GetGoal‐L and GetGoal‐L‐C, was carried out to assess the efficacy of lixisenatide versus placebo as an add‐on treatment to BI ± metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2‐h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control.ResultsPooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference −0.49, 95% confidence interval −0.68 to − 0.30 and white patients least squares mean difference −0.45, 95% confidence interval −0.63 to − 0.26; P = 0.6287). Similarly, no significant difference was found in 2‐h PPG reduction between both groups (least squares mean difference for Asian vs white patients: −3.37 vs −3.93; P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of −0.56% after adjustment of baseline HbA1c level in Asian patients, and −0.41% in white patients.ConclusionsAdding lixisenatide to BI significantly reduced HbA1c and 2‐h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.
Autologous serum skin test reactions in chronic spontaneous urticaria differ from heterologous cell reactions
Authors: Baumann K. , Marcelino J. , Skov P.S. , Santos M.C.P. , Wyroslak I. , Scheffel J. , Altrichter S. , Woetmann A. , Costa C. , Maurer M. 
Published: January 2021

AbstractBackgroundAutoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)‐activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown.ObjectivesTo characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches.MethodsWe determined the rates of ASST+/BT− and ASST−/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD).ResultsThe ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT−: 22%, ASST−/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA−: 18.8% and ASST−/BHRA+: 16.7%) and 31.3% (ASST+/BAT−: 6.3% and ASST−/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P = 0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA−: 18.8%, ASST−/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD−: 10.0% and ASST−/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P = 0.0002).ConclusionsThe ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum‐induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.
Host‐specific preference of some Flavobacteriumpsychrophilum multilocus sequence typing genotypes determines their ability to cause bacterial coldwater disease in coho salmon (Oncorhynchuskisutch)
Authors: Knupp Christopher , Kiupel Matti , Brenden Travis O. , Loch Thomas P. 
Published: January 2021

AbstractFlavobacterium psychrophilum causes bacterial coldwater disease (BCWD) in salmonids, resulting in significant losses worldwide. Several serotyping and genetic studies of F. psychrophilum have suggested some geno‐/serotypes may be either host‐specific or generalistic in nature; however, this association has not been adequately explored in vivo using more natural exposure routes. Herein, F. psychrophilum isolate US19‐COS, originally recovered from coho salmon (Oncorhynchus kisutch) and belonging to multilocus sequence typing clonal complex (CC) CC‐ST9, and isolate US53‐RBT, recovered from rainbow trout (Oncorhynchus mykiss) and belonging to CC‐ST10, were serotyped via PCR, evaluated for proteolytic activity and utilized to determine their median lethal dose in immersion‐challenged coho salmon fingerlings. US19‐COS belonged to serotype 0, hydrolysed casein and gelatin but not elastin, led to fulminant multiorgan infections and elicited severe gross and microscopic pathology. In contrast, US53‐RBT, belonging to serotype 2, hydrolysed all three substrates, but did not lead to detectable infections, disease signs or mortality in any exposed coho salmon despite proving virulent to rainbow trout in previous experiments. This study provides in vivo evidence for potential host specificity of some F. psychrophilum genotypes that can also be serologically distinct, a matter of importance towards better understanding F. psychrophilum disease ecology and epidemiology.
MRI Lesion State Modulates the Relationship Between Serum Neurofilament Light and Age in Multiple Sclerosis
Authors: Rosso Mattia , Healy Brian C. , Saxena Shrishti , Paul Anu , Bjornevik Kjetil , Kuhle Jens , Benkert Pascal , Leppert David , Guttmann Charles , Bakshi Rohit , Weiner Howard L. , Chitnis Tanuja 
Published: January 2021

ABSTRACTBACKGROUND AND PURPOSESerum neurofilament light (sNfL) has been studied as a biomarker of disease activity in multiple sclerosis (MS). Several factors, including age, can influence its dynamics, and several studies have shown that sNfL increases with age in controls. Our objective was to explore the relationship of sNfL and age at different MS disease stages, including remission and after a gadolinium‐enhancing (Gad+) lesion.METHODSWe included 94 patients with MS with annual sNfL measurements performed with a single‐molecule array assay. We used multivariable linear mixed‐effects models with random intercept to test the association between age and sNfL during remission and after a Gad+ lesion (ie, within 90 days after the Gad+ lesion). The model was adjusted for medication use and sex.RESULTSWe report a positive association between sNfL level and age during remission (adjusted estimate = 1.18% yearly increase, 95% CI = .34‐2.03%, P = .008). In contrast, a negative interaction between age and Gad+ lesion status was observed (adjusted estimate = −1.73%, 95% CI = −2.85 to −.58%, P = .004).CONCLUSIONWe propose that younger patients experience a greater elevation in sNfL than older patients in response to Gad+ lesions. Our study provides potential insights into the effects of aging on neuroinflammation in MS.