bluuebunny/crossref_metadata_2025_split huggingface dataset:
Logarithmic-corrected Einstein–Gauss–Bonnet inflation compatible with GW170817
Authors: Venikoudis S. A. , Fronimos F. P. 
Published: March 2021

AbstractIn this paper, we investigate the inflationary phenomenology of an Einstein–Gauss–Bonnet theory with the extension of a logarithmic modified f(R) gravity, compatible with the GW170817 event. The main idea of our work is to study different results for an almost linear Ricci scalar through logarithmic corrections and examine whether such model is viable. First of all, the theoretical framework under slow-roll evolution of the scalar field is presented and also the formalism of the constant-roll evolution making predictions for the non-Gaussianities of the models is developed, since the constant-roll evolution is known to enhance non-Gaussianities. As shown, the non-Gaussianities are of the order $${\mathcal {O}}\sim (10^{-1})$$

O
∼
(

10

-
1

)

. Furthermore, the slow-roll indices and the observational indices of inflation are calculated for several models of interest. As demonstrated, the phenomenological viability of the models at hand is achieved for a wide range of the free parameters and the logarithmic term has a minor contribution to numerical calculations, as expected.
Contracturing Granulomatous Myositis with Recurrent Malignant Thymoma and Myasthenia Gravis: A Case Report
Authors: Luk Ching On , Lo Wai Ting Joyce , Kwok Kitty Yan , Leung Moon Ho , Fong Wing Chi , Cheung Yuk Fai 
Published: March 2021

Contracturing granulomatous myositis (CGM) is a very rare myopathic syndrome where patients present with slowly progressive muscle pain or weakness affecting mainly proximal muscles together with flexion contractures of the limbs. To date, there have only been several case reports of CGM, which have been reported to occur most commonly in association with sarcoidosis. We report a case of CGM associated with recurrent malignant thymoma and myasthenia gravis (MG). A gentleman with history of treated malignant thymoma presented with new onset proximal muscle weakness and pain that later evolved into contractures that persisted despite treatment with steroids and intravenous immunoglobulin. A malignancy workup revealed recurrence of his malignant thymoma warranting chemotherapy treatment. His contractures only resolved after addition of chemotherapy treatment. He later developed clinical features of MG 1 year after his initial elevation in Anti-acetylcholine (Anti-AChR) antibody levels. We postulate CGM to be a paraneoplastic phenomenon of underlying malignant thymoma. Treatment of thymoma together with immunosuppressive therapies led to clinical improvement of our patient’s CGM. The sole elevation of Anti-AChR levels without the accompanying clinical features does not equate to a MG diagnosis, but should raise the clinician’s vigilance for future development of the condition.
Stappen High–Bjørnøya Tectono-Sedimentary Element, Barents Sea
Authors: Tsikalas Filippos , Blaich Olav Antonio , Faleide Jan Inge , Olaussen Snorre 
Published: March 2021

Abstract
The Stappen High–Bjørnøya Tectono-Sedimentary Element (TSE) is located in the western Barents Shelf and is one of the prominent tectonic elements in the area. The Stappen High comprises a shallow platform, and Bjørnøya forms its highest point with exposed outcrops. Modern seismic reflection data of improved quality in the southern part of the TSE and vintage seismic data in the northern portion are utilised. Together with updated geological information at Bjørnøya, the study provides insights into the Paleozoic–early Cenozoic evolution of the Stappen High–Bjørnøya TSE. In this context, we discuss structural inheritance and the rift development, and account for confirmed and potential hydrocarbon systems and plays.
Beyond MPI
Authors: Liu Feilong , Barthels Claude , Blanas Spyros , Kimura Hideaki , Swart Garret 
Published: March 2021

Networkswith Remote DirectMemoryAccess (RDMA) support are becoming increasingly common. RDMA, however, offers a limited programming interface to remote memory that consists of read, write and atomic operations. With RDMA alone, completing the most basic operations on remote data structures often requires multiple round-trips over the network. Data-intensive systems strongly desire higher-level communication abstractions that supportmore complex interaction patterns.
A natural candidate to consider is MPI, the de facto standard for developing high-performance applications in the HPC community. This paper critically evaluates the communication primitives of MPI and shows that using MPI in the context of a data processing system comes with its own set of insurmountable challenges. Based on this analysis, we propose a new communication abstraction named RDMO, or Remote DirectMemory Operation, that dispatches a short sequence of reads, writes and atomic operations to remote memory and executes them in a single round-trip.
Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study
Authors: Mao Jenny T. , Xue Bingye , Fan Sili , Neis Patricia , Qualls Clifford , Massie Larry , Fiehn Oliver 
Published: March 2021

AbstractGrape seed procyanidin extract (GSE) has been shown to exert antineoplastic properties in preclinical studies. Recently, we reported findings from a modified phase I, open-label, dose escalation clinical study conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome, a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Three months of leucoselect phytosome treatment significantly decreased bronchial Ki-67 labeling index (LI), a marker of cell proliferation on the bronchial epithelium. Because GSE is widely used as a supplement to support cardiovascular health, we evaluate the impact of oral leucoselect phytosome on the fasting serum complex lipid metabolomics profiles in our participants. One month of leucoselect phytosome treatment significantly increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the omega-3 polyunsaturated fatty acids (n-3 PUFA) with well-established anticancer properties. Leucoselect phytosome also significantly increased unsaturated phosphatidylcholines (PC), likely from soy phospolipids in the phytosome and functioning as transporters for these PUFAs. Furthermore, 3-month leucoselect phytosome treatment significantly increased serum prostaglandin (PG) E3 (PGE3), a metabolite of EPA with anti-inflammatory and antineoplastic properties. Such increases in PGE3 correlated with reductions of bronchial Ki-67 LI (r = −0.9; P = 0.0374). Moreover, posttreatment plasma samples from trial participants significantly inhibited proliferation of human lung cancer cell lines A549 (adenocarcinoma), H520 (squamous cell carcinoma), DMS114 (small cell carcinoma), and 1198 (preneoplastic cell line). Our findings further support the potential utility of leucoselect phytosome in reducing cardiovascular and neoplastic risks in heavy former and active smokers.Prevention Relevance:In this correlative study of leucoselect phytosome for lung cancer chemoprevention in heavy active and former smokers, we demonstrate for the first time, favorable modulations of n-3PUFA and downstream PGE3 in fasting serum, further supporting the chemopreventive potential of leucoselect phytosome against lung cancer.
CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor Cells and T Cells
Authors: Kumar Sushil , Zeng Zexian , Bagati Archis , Tay Rong En , Sanz Lionel A. , Hartono Stella R. , Ito Yoshinaga , Abderazzaq Fieda , Hatchi Elodie , Jiang Peng , Cartwright Adam N.R. , Olawoyin Olamide , Mathewson Nathan D. , Pyrdol Jason W. , Li Mamie Z. , Doench John G. , Booker Matthew A. , Tolstorukov Michael Y. , Elledge Stephen J. , Chédin Frédéric , Liu X. Shirley , Wucherpfennig Kai W. 
Published: March 2021

Abstract

A number of cancer drugs activate innate immune pathways in tumor cells but unfortunately also compromise antitumor immune function. We discovered that inhibition of CARM1, an epigenetic enzyme and cotranscriptional activator, elicited beneficial antitumor activity in both cytotoxic T cells and tumor cells. In T cells, Carm1 inactivation substantially enhanced their antitumor function and preserved memory-like populations required for sustained antitumor immunity. In tumor cells, Carm1 inactivation induced a potent type 1 interferon response that sensitized resistant tumors to cytotoxic T cells. Substantially increased numbers of dendritic cells, CD8 T cells, and natural killer cells were present in Carm1-deficient tumors, and infiltrating CD8 T cells expressed low levels of exhaustion markers. Targeting of CARM1 with a small molecule elicited potent antitumor immunity and sensitized resistant tumors to checkpoint blockade. Targeting of this cotranscriptional regulator thus offers an opportunity to enhance immune function while simultaneously sensitizing resistant tumor cells to immune attack.

Significance:
Resistance to cancer immunotherapy remains a major challenge. Targeting of CARM1 enables immunotherapy of resistant tumors by enhancing T-cell functionality and preserving memory-like T-cell populations within tumors. CARM1 inhibition also sensitizes resistant tumor cells to immune attack by inducing a tumor cell–intrinsic type 1 interferon response.
This article is highlighted in the In This Issue feature, p. 1861
Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In Vivo
Authors: Foggetti Giorgia , Li Chuan , Cai Hongchen , Hellyer Jessica A. , Lin Wen-Yang , Ayeni Deborah , Hastings Katherine , Choi Jungmin , Wurtz Anna , Andrejka Laura , Maghini Dylan G. , Rashleigh Nicholas , Levy Stellar , Homer Robert , Gettinger Scott N. , Diehn Maximilian , Wakelee Heather A. , Petrov Dmitri A. , Winslow Monte M. , Politi Katerina 
Published: March 2021

Abstract

In lung adenocarcinoma, oncogenic EGFR mutations co-occur with many tumor suppressor gene alterations; however, the extent to which these contribute to tumor growth and response to therapy in vivo remains largely unknown. By quantifying the effects of inactivating 10 putative tumor suppressor genes in a mouse model of EGFR-driven Trp53-deficient lung adenocarcinoma, we found that Apc, Rb1, or Rbm10 inactivation strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2—the strongest drivers of growth in a KRAS-driven model—reduced EGFR-driven tumor growth. These results are consistent with mutational frequencies in human EGFR- and KRAS-driven lung adenocarcinomas. Furthermore, KEAP1 inactivation reduced the sensitivity of EGFR-driven tumors to the EGFR inhibitor osimertinib, and mutations in genes in the KEAP1 pathway were associated with decreased time on tyrosine kinase inhibitor treatment in patients. Our study highlights how the impact of genetic alterations differs across oncogenic contexts and that the fitness landscape shifts upon treatment.

Significance:
By modeling complex genotypes in vivo, this study reveals key tumor suppressors that constrain the growth of EGFR-mutant tumors. Furthermore, we uncovered that KEAP1 inactivation reduces the sensitivity of these tumors to tyrosine kinase inhibitors. Thus, our approach identifies genotypes of biological and therapeutic importance in this disease.
This article is highlighted in the In This Issue feature, p. 1601
ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia—Brief Report
Authors: Reeskamp Laurens F. , Millar John S. , Wu Liya , Jansen Hans , van Harskamp Dewi , Schierbeek Henk , Gipe Daniel A. , Rader Daniel J. , Dallinga-Thie Geesje M. , Hovingh G. Kees , Cuchel Marina 
Published: March 2021

Objective:
The mechanism by which evinacumab, a fully human monoclonal antibody directed against ANGPTL3 (angiopoietin-like 3 protein) lowers plasma LDL (low-density lipoprotein) cholesterol levels in patients with homozygous familial hypercholesterolemia is unknown. We investigated apoB (apolipoprotein B) containing lipoprotein kinetic parameters in patients with homozygous familial hypercholesterolemia, before and after treatment with evinacumab.

Approach and Results:

Four patients with homozygous familial hypercholesterolemia underwent apoB kinetic analyses in 2 centers as part of a substudy of a trial evaluating the efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia. The enrichment of apoB with the stable isotope (5,5,5-
2
H
3
)-Leucine was measured in VLDL (very LDL), IDL (intermediate-density lipoprotein), and LDL at different time points before and after intravenous administration of 15 mg/kg evinacumab. Evinacumab lowered LDL-cholesterol by 59±2% and increased IDL apoB and LDL apoB fractional catabolic rate in all 4 homozygous familial hypercholesterolemia subjects, by 616±504% and 113±14%, respectively. VLDL-apoB production rate decreased in 2 of the 4 subjects.

Conclusions:
In this small study, ANGPTL3 inhibition with evinacumab is associated with an increase in the fractional catabolic rate of IDL apoB and LDL apoB, suggesting that evinacumab lowers LDL-cholesterol predominantly by increasing apoB-containing lipoprotein clearance from the circulation. Additional studies are needed to unravel which factors are determinants in this biological pathway.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04722068.
Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation
Authors: Xu Zheng , Liang Ying , Delaney M. Keegan , Zhang Yaping , Kim Kyungho , Li Jing , Bai Yanyan , Cho Jaehyung , Ushio-Fukai Masuko , Cheng Ni , Du Xiaoping 
Published: March 2021

Objective:

Despite the importance of reactive oxygen species (ROS) and NOX (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) 2 in platelet activation and in vivo thrombosis, it is unclear how ROS and NOX2 play a role in platelet activation and why NOX2 deficiencies in humans and mice do not affect hemostasis. Outside-in signaling of integrin α
IIb
β
3
mediates platelet response to shear stress, secondary platelet activation, and thrombus expansion and is critical to thrombosis but dispensable for hemostasis. We studied the mechanisms of platelet ROS generation, ROS-mediated platelet response, and the role of ROS in integrin α
IIb
β
3
outside-in signaling.

Approach and Results:

ROS generation in activated platelets was low and slow without shear but was robust under shear. Shear-enhanced ROS generation and activation of p47phox, an important regulatory subunit of NOX2, were diminished by the integrin antagonist integrilin or β
3
knockout, and by Gα
13
knockout or blocking the Gα
13
-β
3
interaction. Resting platelets spreading on integrin ligand fibrinogen also Gα
13
-dependently stimulated ROS generation and p47phox activation. Hence, Gα
13
-mediated outside-in signaling induces NOX2 activation and ROS generation which is greatly enhanced by shear. Outside-in NOX2 activation requires Src, phosphoinositide 3-kinase and Akt downstream of Gα
13
. Importantly, NOX2-knockout platelets showed defective ROS generation, reduced platelet spreading without shear, and reduced platelet adhesion and thrombus volume on collagen and VWF (von Willibrand factor) under shear, whereas ROS inhibition diminished activation of tyrosine kinase Syk.

Conclusions:
Outside-in signaling activates the mainly NOX2-mediated ROS generation, which mediates Syk-dependent secondary platelet activation, adhesion, and thrombosis with minimal effect on hemostasis.
Abstract MP9: Incidence and Outcomes of Posterior Circulation Involvement in Moyamoya Disease
Authors: Tigchelaar Seth S , Wang Allan , Li Yiping , Steinberg Gary 
Published: March 2021

Moyamoya disease (MMD) is a progressive, occlusive disease of the internal carotid arteries and their proximal branches, with the subsequent development of an abnormal vascular network of small, weak blood vessels that are prone to rupture. Steno-occlusive changes in the posterior cerebral arteries (PCA) may contribute to worse outcomes in MMD patients, however, there is a paucity of information on the incidence and natural history of MMD patients with PCA disease.
We retrospectively reviewed the charts of patients with MMD treated between 1987 and 2019. Demographics, peri-operative outcomes, and radiological phenotypes were recorded for 450 patients. PCA disease was scored as either 0 (no disease), 1 (mild), 2 (moderate), or 3 (severe, or occluded).
Out of 450 patients, 164 (34.4%) had concurrent PCA disease. In patients with PCA disease, the extent of occlussion was mild in 56 (34%), moderate in 41 (25%), and severe in 67 (40.9%) patients. In total, there were 319 females (70.9%), with a higher proportion of female MMD patients having severe or moderate PCA disease (p=0.038). Patients with severe and moderate PCA disease had higher Suzuki grades (p<0.0001), more extensive collateral angiopathy (p<0.0001), more frequent cerebrovascular accidents on presentation (p=0.012), higher hemodynamic scores (p=0.022), and a greater frequency of post-operative ischemic complications (p=0.019). Peak modified Rankin Scale (mRS) scores were higher in patients with any severity of PCA disease (p=0.0006).
Over a mean follow-up of 6.94±4.16 years, 28 patients (8.86%) developed new or progressive PCA disease. Bilateral disease was present in 66 patients (14.7%) and was associated with higher Suzuki grades (p<0.0001), more extensive collateral angiopathy (p<0.0001), and greater post-operative ischemic complications (p=0.011). Peak mRS scores were higher in patients with bilateral disease compared to patients with no PCA disease (p<0.0001).
PCA disease involvement is associated with higher rates of ischemic peri-operative complications and poor functional outcomes likely due to reduced collateral flow. Progression of PCA disease is not uncommon. Future studies are needed to assess the impact of PCA disease progression on long-term outcomes.
Abstract P198: Daily Step Count at Two Months is the Strongest Predictor of Daily Steps at One Year Post-Stroke
Authors: Handlery Reed , Regan Elizabeth , Hainline Garrett , Fritz Stacy 
Published: March 2021

For survivors of stroke, walking can improve endurance, community participation and decrease risk of subsequent stroke. Unfortunately, survivors take 4000 fewer steps per day compared to other adults. Early identification of survivors prone to long-term inactivity would be valuable, as interventions could be implemented to improve physical activity (PA) levels and reduce subsequent stroke risk.
Secondary data from the Locomotor Experience Applied Post Stroke (LEAPS) trial was used. Included participants had walking speeds of <0.80 m/s at 2 months post-stroke. Daily steps were assessed at 2 months and 1 year post-stroke using an activity monitor. Stepwise regression was used to predict daily step counts at 1 year based on modifiable (walking speed, endurance, balance, balance confidence, daily step counts) and nonmodifiable (age at time of stroke, gender, race, ethnicity, initial stroke severity, side of stroke and LEAPS intervention group) factors.

Data was available for 206 survivors, mean age=63 (13) years, 43% female (88/206), mean walking speed=.41 (.22) m/s, mean step count=2922 (2749) steps per day. The strongest predictor of daily steps at 1 year was daily steps at 2 months (p=<0.001, adjusted R
2
=.34). For every 1-step increase at 2 months, there was an increase of .54 (95% CI .38, .71) steps at 1 year. The next strongest predictor was walking endurance (Six Minute Walk), which significantly increased adjusted R
2
by .02 (p=.009). For every 1-meter increase in Six Minute Walk distance at 2 months, there was an increase of 8 (95% CI 2, 14) steps at 1 year. Together, baseline steps and Six Minute Walk distance explained 36% of the variance in daily steps at 1 year. No other factors significantly added to the prediction model.

Daily steps at 2 months post-stroke was the strongest predictor (explaining 34% of the variance) of steps at 1 year. Survivors with low daily steps early after stroke may benefit from targeted walking interventions to increase PA and long term health outcomes.
Abstract P332: Cerebral Small Vessel Disease Score in CADASIL: Relationships to Cognitive Dysfunctions
Authors: Schoemaker Dorothee , Zuluaga Yesica , Velilla Lina , Ospina Carolina , Lopera Francisco , Arboleda-Velasquez Joseph , Quiroz Yakeel 
Published: March 2021

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition.
We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols.
Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B).
These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.