bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction immunosuppression strategies and long‐term outcomes after heart transplantation
Authors: Nozohoor Shahab , Stehlik Josef , Lund Lars H. , Ansari David , Andersson Bodil , Nilsson Johan 
Published: April 2020

AbstractAlthough the use of induction therapy has reduced the risk of acute rejection after heart transplantation, its use may be associated with other adverse outcomes. We aimed to examine the effect of no induction (NoInd), induction with basiliximab (BAS), or induction with antithymocyte globulin (ATG) on outcome after heart transplantation. We analyzed data from the International Society for Heart and Lung Transplantation (ISHLT) registry for adult heart transplants performed between 2000 and 2013. The primary outcome was cumulative all‐cause mortality, and the secondary outcome was cause‐specific death. We identified 27 369 transplants whose recipients received NoInd (n = 15 688), ATG (n = 6830), or BAS (n = 4851). Over a median follow‐up of 1497 days, overall 30‐day mortality was 5% and 1‐year mortality was 11%. Survival after transplant was similar in patients treated with NoInd compared with ATG. The survival was improved using NoInd compared with BAS (log‐rank P = .040), adjustment HR = 1.11 (95% CI, 1.04‐1.19). Compared to NoInd, BAS was associated with higher risk of graft failure‐related deaths, HR = 1.27 (95% CI, 1.02‐1.58), and ATG was associated with higher risk of malignancy‐related deaths, HR = 1.18 (95% CI, 1.01‐1.39). Survival of patients who received NoInd was similar to ATG and better compared with BAS. Further, the use of ATG may be associated with increased malignancy‐related mortality, compared with NoInd.
Myosin affects the structure and volatile flavour compounds binding of G‐actin in grass carp
Authors: Lin Rufei , Xiao Xiao , Yue Yi , Wang Ying , Pan Daodong , Wang Daoying , Yang Qiuli , He Jun , Cao Jinxuan 
Published: April 2020

SummaryThe effects of myosin (0, 0.2, 0.4, and 0.6 mg mL−1) on the protein structure and volatiles adsorption capacity of G‐actin from grass carp were investigated. The results showed that the myosin addition increased the surface hydrophobicity and sulfhydryl contents of G‐actin. The Raman spectroscopy analysis showed that the α‐helix and β‐sheet of G‐actin were converted into β‐turn and random coil with 0.2 and 0.4 mg mL−1 of myosin, while only the β‐turn content increased with 0.6 mg mL−1 of myosin. The GC‐MS analysis indicated that with myosin addition, the adsorption capacities of G‐actin on alcohols (1‐pantanol, 1‐hexanol, 1‐octen‐3‐ol, and 1‐octanol) and ketones (2‐pentanone, 2‐heptanone, 2‐octanone, and 2‐nonanone) were enhanced; meanwhile, the binding of G‐actin to aldehydes (pentanal, hexanal, octanal, and nonanal) was weakened. It was probably due to the formation of actomyosin, and also the excess myosin when treated with high concentrations (0.4 and 0.6 mg mL−1) of myosin.
Evaluation of stroke incidence with duty‐cycled multielectrode‐phased radiofrequency ablation of persistent atrial fibrillation results of the VICTORY AF Study
Authors: Hummel John , Verma Atul , Calkins Hugh , Schwamm Lee H. , Gress Daryl , Wells Darryl , Souza Joseph , Hokanson Robert B. , Hemingway Lauren , Stromberg Kurt , Hoyt Robert , Wickliffe Andrew , DeLurgio David , Boersma Lucas 
Published: April 2020

AbstractIntroductionThe VICTORY AF Study was designed to evaluate the risk of the procedure and/or device‐related strokes in patients with PersAF on warfarin undergoing ablation with a phased radiofrequency (RF) system.MethodsThe VICTORY AF trial was a prospective, multicenter, single‐arm, investigational study. PersAF patients on vitamin K antagonism without major structural heart disease or history of stroke/transient ischemic attack undergoing phased RF ablation for atrial fibrillation (AF) were included. The primary outcome was the incidence of the procedure and/or device‐related stroke within 30 days of the ablation by a board‐certified neurologist's assessment. The secondary outcomes were an acute procedural success, 6 months effectiveness (defined as the reduction in AF/atrial flutter episodes lasting ≥10 minutes by 48‐hour Holter 6 months postablation) and the number of patients with pulmonary vein (PV) stenosis.ResultsA total of 129 (108 PersAF, 21 long‐standing PersAF) patients were treated (mean age: 60.6 ± 7.7; 79.8% male, 54.3% CHA2Ds2‐VASc score ≥ 2). Two nondisabling strokes were reported (1.6%); one before discharge and the second diagnosed at the 30‐day visit. Due to slow enrollment, the study was terminated before reaching the 95% one‐sided upper confidence boundary for stroke incidence. Acute procedural success was 93.8%, and at 6 months, 72.8% of patients demonstrated ≥90% reduction in AF burden, 78.9% were off all antiarrhythmic drugs. There were no patients with PV stenosis of greater than 70%.ConclusionsVICTORY AF demonstrated a 1.6% incidence of stroke in PersAF undergoing ablation with a phased RF system which did not meet statistical confidence due to poor enrollment. The secondary outcomes suggest comparable efficacy to phased RF in the tailored treatment of permanent AF trial. Rigorous clinical evaluation of the stroke risk of new AF ablation technologies as well as restriction to Vitamin K antagonist anticoagulation appears to be unachievable goals in a clinical multicenter IDE trial of AF ablation in the current era.
Clinical value of multiorgan damage in hypertensive crises: A prospective follow‐up study
Authors: Ma Hongkun , Jiang Mengdi , Fu Zongjie , Wang Zhiyu , Shen Pingyan , Shi Hao , Feng Xiaobei , Chen Yongxi , Ding Xiaoyi , Wu Zhiyuan , Zhang Wen 
Published: April 2020

AbstractHypertensive crises are associated with high rates of target organ complications and poor outcomes. A recent shift from the definition of malignant hypertension to hypertension‐multiorgan damage (MOD) contributes to the diagnosis and management of hypertensive crises. Here, we prospectively included 166 adult (≥18 years old) patients with hypertensive crises (blood pressure >180/120 mm Hg). Target organs and causes of hypertension were assessed. Patients who were diagnosed with malignant hypertensive retinopathy, the absence of malignant hypertensive retinopathy but the presence of damage to at least 3 organs, and the absence of both retinopathy and MOD were classified as the malignant hypertension (n = 48), hypertension‐MOD (n = 42), and hypertension without MOD (n = 76) groups, respectively. Patients were followed to evaluate renal and cardiovascular prognoses. At baseline, patients with malignant hypertension had worse renal function, higher level of albuminuria, and more severe microvascular damage than those with hypertension‐MOD. Both had similar proportions of malignant arteriolar nephrosclerosis (83% vs 64%), left ventricular hypertrophy (90% vs 88%), abnormal repolarization (71% vs 60%), and left ventricular dysfunction (12% vs 21%). At the twenty months of follow‐up, both the malignant hypertension and hypertension‐MOD groups had similar blood pressure control rates and proteinuria. Both groups had worse renal outcomes than the hypertension without MOD group (P = .002). Patients with hypertension‐MOD (HR = 0.67, [95% CI: 0.30‐1.46], P = .31) had similar renal event‐free survival than patients with MHT after adjustments of age, sex, blood pressure, and proteinuria control. These results suggest that in hypertensive crises, both malignant hypertension and hypertension‐MOD have impact on adverse renal outcomes.
Tofacitinib in psoriatic arthritis patients: skin signs and symptoms and health‐related quality of life from two randomized phase 3 studies
Authors: Merola J.F. , Papp K.A. , Nash P. , Gratacós J. , Boehncke W.H. , Thaçi D. , Graham D. , Hsu M‐A. , Wang C. , Wu J. , Young P. 
Published: April 2020

AbstractBackgroundPsoriatic arthritis (PsA) is a chronic, systemic immune‐mediated inflammatory musculoskeletal disease. The onset of dermatologic symptoms often precedes rheumatic manifestations. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA that has been shown to improve dermatologic symptoms in patients with PsA.ObjectivesTo investigate the efficacy of tofacitinib in improving dermatologic endpoints in adult patients with active PsA.MethodsThis analysis included data from two placebo‐controlled, double‐blind, phase 3 studies in patients with active PsA and an inadequate response (IR) to ≥1 conventional synthetic disease‐modifying antirheumatic drug (csDMARD) who were tumor necrosis factor inhibitor (TNFi)‐naïve (OPAL Broaden; NCT01877668) or an IR to ≥1 TNFi (OPAL Beyond; NCT01882439). Patients had active plaque psoriasis at screening and received a stable dose of one csDMARD during the study. Patients were randomized to tofacitinib 5 mg twice daily (BID), 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only) or placebo (to Month 3). Dermatologic endpoints: Psoriasis Area and Severity Index (PASI) total score; PASI90 overall; PASI75 and PASI90 by baseline PASI severity; Physician’s Global Assessment of Psoriasis; Nail Psoriasis Severity Index; Dermatology Life Quality Index total and sub‐dimension scores; Itch Severity Item; and Patient’s Global Joint and Skin Assessment‐Visual Analog Scale‐Psoriasis question.ResultsIn patients with active PsA, including those stratified by mild or moderate/severe dermatologic symptoms, greater improvements from baseline and percentage of responders were observed in tofacitinib‐treated patients vs. placebo for the majority of analyzed dermatologic endpoints at Months 1 and 3, and improvements were maintained to Month 12 in OPAL Broaden and Month 6 in OPAL Beyond. Similar effects were observed in adalimumab‐treated patients vs. placebo in OPAL Broaden across dermatologic endpoints.ConclusionsTofacitinib provides a treatment option for patients with active PsA, including the burdensome dermatologic symptoms of PsA.
Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease
Authors: Bjørnestad E. Ø. , Olset H. , Dhar I. , Løland K. , Pedersen E. K. R. , Svingen G. F. T. , Svardal A. , Berge R. K. , Ueland P. M. , Tell G. S. , Nilsen D. W. T. , Nordrehaug J. E. , Nygaard E. , Nygård O. 
Published: April 2020

AbstractBackgroundThe carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine‐N‐oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modifications by riboflavin status.MethodsBy Cox modelling, risk associations were examined amongst 4098 patients (71.8% men) with suspected stable angina pectoris. Subgroup analyses were performed according to median plasma riboflavin.ResultsDuring a median follow‐up of 4.9 years, 336 (8.2%) patients experienced an AMI. The age‐ and sex‐adjusted hazard ratio (HR) (95% CI) comparing the 4th vs. 1st TML quartile was 2.19 (1.56–3.09). Multivariable adjustment for traditional cardiovascular risk factors and indices of renal function only slightly attenuated the risk estimates [HR (95% CI) 1.79 (1.23–2.59)], which were particularly strong amongst patients with riboflavin levels above the median (Pint = 0.035). Plasma TML and TMAO were strongly correlated (rs = 0.41; P < 0.001); however, plasma TMAO was not associated with AMI risk in adjusted analyses [HR (95% CI) 0.81 (0.58–1.14)]. No interaction between TML and TMAO was observed.ConclusionAmongst patients with suspected stable angina pectoris, plasma TML, but not TMAO, independently predicted risk of AMI. Our results motivate further research on metabolic processes determining TML levels and their potential associations with cardiovascular disease. We did not adjust for multiple comparisons, and the subgroup analyses should be interpreted with caution.
The factors related to decreases in masticatory performance and masticatory function until swallowing using gummy jelly in subjects aged 20‐79 years
Authors: Ohno Keitaro , Fujita Yuko , Ohno Yoma , Takeshima Tomohiro , Maki Kenshi 
Published: April 2020

AbstractBackgroundThere is growing international interest in the prevention of decreased oral function for managing oral health in older people.ObjectiveThe aims of the present study were to identify factors related to decreases in masticatory performance and masticatory function until swallowing in subjects aged 20‐79 years old.MethodsA total of 152 subjects, ranging in age from 20 to 79 years, were divided into six groups according to their chronological age: 20‐29, 30‐39, 40‐49, 50‐59, 60‐69 and 70‐79 years. Grip strength, maximum occlusal force, maximum tongue pressure, masticatory performance and swallowing threshold were measured in all subjects. Masticatory performance and swallowing threshold were determined according to the concentration of dissolved glucose obtained from gummy jellies; decreased masticatory performance and decreased swallowing threshold were defined as glucose concentrations in the lowest 20th percentile. A multivariate binary logistic regression analysis was used to identify factors associated with decreased masticatory performance and decreased swallowing threshold. A self‐administered lifestyle questionnaire was also completed.ResultsLogistic regression analyses revealed that factors related to decreased masticatory performance included use of more than one kind of medicine for treating chronic diseases and removable denture use, while factors related to decreased swallowing threshold included eating between meals once or more per day, poorer mental health and decreased saliva flow.ConclusionsDifferent factors are related to decreased masticatory performance and decreased swallowing threshold, although both of these phenomena are closely associated with general health status.
Static and Fatigue Loading of Veneered Implant‐Supported Fixed Dental Prostheses
Authors: Rayyan Mohammad M. , Abdallah Jihad , Segaan Lucette G. , Bonfante Estevam A. , Osman Essam 
Published: April 2020

AbstractPurposeThis study aimed to compare the load to failure and the probability of survival of porcelain fused to zirconia (PFZ) three‐unit, implant‐supported, fixed dental prostheses (FDPs) to those of indirect composites veneered to either zirconia (CVZ) or milled fiber‐reinforced composite (FRC) frameworks under static and fatigue loading.Materials and MethodsOne‐hundred and twenty posterior three‐unit FDP (second premolar pontic) frameworks were fabricated via milling from a single Standard Tessellation Language (STL) file. The FDPs were divided into three groups. Each group (n = 40) was subjected to static (n = 20) and fatigue (n = 20) loading tests, as follows: (1) PFZ: zirconia framework layered with porcelain veneer; (2) CVZ: zirconia framework veneered with indirect composite resin; and (3) FRC: FRC framework veneered with indirect composite resin. After porcelain veneering onto sintered zirconia frameworks, or resin composite veneering onto zirconia or FRC frameworks, FDPs were cemented on their abutments using self‐adhesive resin cement. After thermal cycling, half of the FDPs were subjected to an accelerated fatigue test. The other half of the FDPs were subjected to single load‐to‐failure (SLF) testing at a crosshead speed (1 mm/min). Lifetime analysis was conducted to determine the probability of survival, and fractographic analysis was performed.ResultsSignificant differences were observed among the studied groups for SLF with the highest characteristic strength values observed for PFZ (2154 N), followed by 1905.47 N for CVZ and 1679.56 N for FRC. The probability of survival for 100,000 cycles at 500 N was the highest for FRC (98%) and CVZ (100%) and was significantly lower for PFZ (88%). Different fracture patterns were observed in the fractography.ConclusionsIn fatigue testing, which simulates masticatory function better than static tests, a higher probability of survival was observed for FRC and CVZ than for PFZ. Framework fractures were not observed only for the FRC group, indicating that chairside repair with the addition of indirect composite could be performed for continued function.
Being English in multilingual South Africa
Authors: Coetzee‐Van Rooy Susan 
Published: April 2020

AbstractThe multilingual repertoires of African home language and bilingual Afrikaans‐English speakers in South Africa have been investigated comprehensively in the recent past. Less attention has been paid to the language repertoires of English home language speakers. Very little is known about the nature of their repertoires and their attitudes towards the languages in their repertoires. These Inner Circle users of English are immersed in a deeply multilingual Outer Circle society where most individuals know at least two languages and the majority of the citizens know more than four languages. The use of English as a home language is also expanding in this context. In this paper, the language repertoires of urban English home language students that participated in a longitudinal language repertoire survey and a group who created language portraits are examined with a view to understand the nature of their language repertoires better. The main finding is that being English in multilingual South Africa means to be at least bilingual with a multilingual mindset. English home language repertoires in South Africa therefore differ from English home language repertoires in Inner Circle contexts like the USA and Australia; and from Outer Circle contexts like Kenya.
The gut hormone secretin triggers a gut–brown fat–brain axis in the control of food intake
Authors: Schnabl Katharina , Li Yongguo , Klingenspor Martin 
Published: April 2020

New Findings
What is the topic of this review?
Brown fat's role in meal‐associated thermogenesis and the related consequences for energy balance regulation with a focus on the gut hormone secretin, which has been identified as the endocrine molecular mediator of meal‐associated brown fat thermogenesis.
What advances does it highlight?
The finding of the secretin‐induced gut–brown fat–brain axis creates new opportunities to manipulate brown fat and thereby energy balance in a natural way while living in a thermoneutral environment. The role of brown fat as a mere catabolic heater organ needs to be revised and more attention should be directed towards the regulatory role of brown fat beyond energy expenditure.
AbstractBrown fat research concentrates on the energy expenditure function of this heating organ, whereas previous evidence for a role of brown fat in regulating energy intake has been mostly neglected. Ingestion of a single mixed meal activates human brown fat thermogenesis to the same degree as cold. In mice, activation of brown fat thermogenesis with a β3‐adrenergic receptor agonist inhibits food intake. Pharmacological β‐blockade, however, inhibits neither meal‐associated thermogenesis nor food intake. We recently identified the gut hormone secretin as a non‐adrenergic activator of brown fat. In vivo, secretin treatment acutely increases energy expenditure and inhibits food intake in wild‐type, but not in uncoupling protein 1 (UCP1)‐knockout (KO) mice, which lack thermogenic brown fat function. Concurrently, secretin alters gene expression of melanocortinergic peptides of hypothalamic neurons in wild‐type mice, but not UCP1‐KO. Blocking endogenous secretin with a neutralizing antibody attenuates brown fat thermogenesis during refeeding, increases food intake of mice, and alters ad libitum feeding behaviour. Taken together, these findings demonstrate that secretin triggers an endocrine gut–brown adipose tissue–brain axis in the control of satiation. We hypothesize that meal‐associated activation of brown adipose tissue thermogenesis induced by secretin results in a rise in brain temperature and increased melanocortinergic signalling. Taken together, brown fat is not a mere heating organ dissipating excess calories but also involved in gut–brain communication in the control of food intake.
A Humanized Lym-1 CAR with Novel DAP10/DAP12 Signaling Domains Demonstrates Reduced Tonic Signaling and Increased Antitumor Activity in B-Cell Lymphoma Models
Authors: Zheng Long , Ren Luqing , Kouhi Aida , Khawli Leslie A. , Hu Peisheng , Kaslow Harvey R. , Epstein Alan L. 
Published: April 2020

AbstractPurpose:The murine Lym-1 mAb targets a discontinuous epitope (Lym-1 epitope) on several subtypes of HLA-DR, which is upregulated in a majority of human B-cell lymphomas and leukemias. Unlike CD19, the Lym-1 epitope does not downregulate upon crosslinking, which may provide an advantage as a target for CAR T-cell therapy. Lym-1 CAR T cells with a conventional 4-1BB and CD3ζ (BB3z) signaling domain exhibited impaired ex vivo expansion. This study aimed to identify the underlying mechanisms and develop strategies to overcome this effect.Experimental Design:A functional humanized Lym-1 antibody (huLym-1-B) was identified and its scFv form was used for CAR design. To overcome observed impaired expansion in vitro, a huLym-1-B CAR using DAP10 and DAP12 (DAP) signaling domains was evaluated for ex vivo expansion and in vivo function.Results:Impaired expansion in huLym-1-B-BB3z CAR T cells was shown to be due to ligand-dependent suboptimal CAR signaling caused by interaction of the CAR binding domain and the surface of human T cells. Using the novel DAP signaling domain construct, the effects of suboptimal CAR signaling were overcome to produce huLym-1-B CAR T cells with improved expansion ex vivo and function in vivo. In addition, the Lym-1 epitope does not significantly downregulate in response to huLym-1-B-DAP CAR T cells both ex vivo and in vivo.Conclusions:DAP intracellular domains can serve as signaling motifs for CAR, and this new construct enables nonimpaired production of huLym-1-B CAR T cells with potent in vivo antitumor efficacy.
Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer
Authors: Tsujikawa Takahiro , Crocenzi Todd , Durham Jennifer N. , Sugar Elizabeth A. , Wu Annie A. , Onners Beth , Nauroth Julie M. , Anders Robert A. , Fertig Elana J. , Laheru Daniel A. , Reiss Kim , Vonderheide Robert H. , Ko Andrew H. , Tempero Margaret A. , Fisher George A. , Considine Michael , Danilova Ludmila , Brockstedt Dirk G. , Coussens Lisa M. , Jaffee Elizabeth M. , Le Dung T. 
Published: April 2020

Abstract

Purpose:
Two studies in previously treated metastatic pancreatic cancer have been completed combining GVAX pancreas vaccine (GM-CSF–secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes–expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B).

Patients and Methods:
Patients with pancreatic adenocarcinoma who received one prior therapy for metastatic disease and RECIST measurable disease were randomized 1:1 to receive treatment on Arm A or Arm B. The primary objective was to compare overall survival (OS) between the arms. Additional objectives included assessment of progression-free survival, safety, tumor responses, CA19-9 responses, and immunologic correlates.

Results:
Ninety-three patients were treated (Arm A, 51; Arm B, 42). The median OS in Arms A and B were 5.9 [95% confidence interval (CI), 4.7–8.6] and 6.1 (95% CI, 3.5–7.0) months, respectively, with an HR of 0.86 (95% CI, 0.55–1.34). Objective responses were seen in 3 patients using immune-related response criteria (4%, 2/51, Arm A; 2%, 1/42, Arm B). The grade ≥3 related adverse event rate, whereas higher in Arm A (35.3% vs. 11.9%) was manageable. Changes in the microenvironment, including increase in CD8+ T cells and a decrease in CD68+ myeloid cells, were observed in long-term survivors in Arm A only.

Conclusions:
Although the study did not meet its primary endpoint of improvement in OS of Arm A over Arm B, the OS was comparable with standard therapy. Objective responses and immunologic changes in the tumor microenvironment were evident.