bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
Authors: Hall Erin M , Yin Dwight E , Goyal Rakesh K , Ahmed Atif A , Mitchell Grace S , St. Peter Shawn D , Flatt Terrie G , Ahmed Ibrahim A , Li Weijie , Hendrickson Richard J , August Keith J , Myers G Doug 
Published: January 2021

BackgroundTisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in the course during clinical trials due to concern for potential negative effect on efficacy and persistence. However, earlier CRS intervention is now viewed more favorably. Earlier intervention and consistency in management between providers may promote broader use of tisagenlecleucel, including potential curative therapy in patients who require remission and recovery of hematopoiesis for management of severe infection.Main bodyPatient 1 was diagnosed with B-ALL at 23 years old. Fourteen days before tisagenlecleucel infusion, the patient developed fever and neutropenia and was diagnosed with invasive Mucorales infection and BK virus hemorrhagic cystitis. Aggressive measures were instituted to control infection and to manage prolonged cytopenias during CAR-T cell manufacturing. Adverse events, including CRS, were manageable despite elevated inflammatory markers and active infection. The patient attained remission and recovered hematopoiesis, and infections resolved. The patient remains in remission ≥1 year postinfusion.Patient 2 was diagnosed with pre–B-ALL at preschool age. She developed severe septic shock 3 days postinitiation of lymphodepleting chemotherapy. After receiving tisagenlecleucel, she experienced CRS with cardiac dysfunction and extensive lymphadenopathy leading to renovascular compromise. The patient attained remission and was discharged in good condition to her country of origin. She remained in remission but expired on day 208 postinfusion due to cardiac arrest of unclear etiology.ConclusionsInfusion was feasible, and toxicity related to tisagenlecleucel was manageable despite active infections and concurrent inflammation, allowing attainment of remission in otherwise refractory pediatric/young adult ALL. This may lead to consideration of tisagenlecleucel as a potential curative therapy in patients with managed active infections.
Irregular pulsation of intracranial unruptured aneurysm detected by four-dimensional CT angiography is associated with increased estimated rupture risk and conventional risk factors
Authors: Zhang Jianjian , Li Xiao , Zhao Bing , Zhang Jin , Sun Beibei , Wang Lingling , Ding Shenghao , Liu Xiangyu , Yan Jing , Mossa-Basha Mahmud , Liu Xiaosheng , Wan Jieqing , Zhao Huilin , Xu Jianrong , Zhu Chengcheng 
Published: January 2021

BackgroundIntracranial aneurysms (IAs) are common in the population and current imaging-based rupture risk assessment needs to be refined. We aimed to use four-dimensional CT angiography (4D-CTA) to investigate the associations of irregular pulsation of IAs with conventional risk factors and the estimated rupture risk.MethodsOne hundred and five patients with 117 asymptomatic IAs underwent 4D-CTA. Geometric and morphologic parameters were measured and the presence of irregular pulsation (defined as a temporary focal protuberance ≥1 mm on more than three successive frames) was identified on 4D-CTA movies. One- and 5 year aneurysm rupture risk were estimated using UCAS and PHASES calculators. Univariate and multivariate analyses were performed to investigate the conventional risk factors associated with irregular pulsation.ResultsIrregular pulsation was observed in 41.0% (48/117) of IAs. Aneurysm size (OR=1.380, 95% CI 1.165 to 1.634), irregular shape (OR=3.737, 95% CI 1.108 to 12.608), and internal carotid artery location (OR=0.151, 95% CI 0.056 to 0.403) were independently associated with irregular pulsation (P<0.05). Aneurysms with irregular pulsation had more than a 6-fold higher estimated rupture risk (1- and 5-year risk [95% CI], 1.56% [0.42%–3.91%], and 2.40% [1.30%–4.30%], respectively) than aneurysms without irregular pulsation (0.23% [0.14%–0.78%] and 0.40% [0.40%–1.30%], respectively) (P<0.001).ConclusionsIAs with irregular pulsation are associated with larger size, irregular-shape, and non-ICA origin, and have more than a 6-fold higher estimated 1- and 5-year rupture risk than aneurysms without irregular pulsation. Irregular pulsation should be validated in future longitudinal studies to determine its predictive value for aneurysm growth and rupture.
Short-term association among meteorological variation, outdoor air pollution and acute bronchiolitis in children in a subtropical setting
Authors: Leung Shuk Yu , Lau Steven Yuk Fai , Kwok Ka Li , Mohammad Kirran N. , Chan Paul Kay Sheung , Chong Ka Chun 
Published: January 2021

ObjectivesTo examine the association among acute bronchiolitis-related hospitalisation in children, meteorological variation and outdoor air pollution.MethodsWe obtained the daily counts of acute bronchiolitis-related admission of children≤2 years old from all public hospitals, meteorological data and outdoor air pollutants’ concentrations between 1 January 2008 and 31 December 2017 in Hong Kong. We used quasi-Poisson generalised additive models together with distributed lag non-linear models to estimate the associations of interest adjusted for confounders.ResultsA total of 29 688 admissions were included in the analysis. Increased adjusted relative risk (ARR) of acute bronchiolitis-related hospitalisation was associated with high temperature (ambient temperature and apparent temperature) and was marginally associated with high vapour pressure, a proxy for absolute humidity. High concentration of NO2 was associated with elevated risk of acute bronchiolitis admission; the risk of bronchiolitis hospitalisation increased statistically significantly with cumulative NO2 exposure over the range 66.2–119.6 µg/m3. For PM10, the significant effect observed at high concentrations appears to be immediate but not long lasting. For SO2, ARR increased as the concentration approached the 75th percentile and then decreased though the association was insignificant.ConclusionsAcute bronchiolitis-related hospitalisation among children was associated with temperature and exposure to NO2 and PM10 at different lag times, suggesting a need to adopt sustainable clean air policies, especially to target pollutants produced by motor vehicles, to protect young children’s health.
Rosemary extract activates AMPK, inhibits mTOR and attenuates the high glucose and high insulin-induced muscle cell insulin resistance
Authors: Shamshoum Hesham , Vlavcheski Filip , MacPherson Rebecca E.K. , Tsiani Evangelia 
Published: January 2021

Impaired action of insulin in skeletal muscle, termed insulin resistance, leads to increased blood glucose levels resulting in compensatory increase in insulin levels. The elevated blood glucose and insulin levels exacerbate insulin resistance and contribute to the pathogenesis of type 2 diabetes mellitus. In previous studies we found attenuation of free fatty acid-induced muscle cell insulin resistance by rosemary extract (RE). In the present study we investigated the effects of RE on high glucose (HG) and high insulin (HI)-induced muscle cell insulin resistance. Exposure of L6 myotubes to 25 mmol/L glucose and 100 nmol/L insulin for 24 h, to mimic hyperglycemia and hyperinsulinemia, abolished the acute insulin-stimulated glucose uptake, increased the serine phosphorylation of IRS-1 and the phosphorylation/activation of mTOR and p70S6K. Treatment with RE significantly improved the insulin-stimulated glucose uptake and increased the acute insulin-stimulated tyrosine phosphorylation while reducing the HG+HI-induced serine phosphorylation of IRS-1 and phosphorylation of mTOR and p70S6K. Additionally, treatment with RE significantly increased the phosphorylation of AMPK, its downstream effector ACC and the plasma membrane GLUT4 levels. Our data indicate a potential of RE to counteract muscle cell insulin resistance and more studies are required to investigate its effectiveness in vivo. Novelty: RE phosphorylated muscle cell AMPK and ACC under both normal and HG+HI conditions. The HG+HI-induced serine phosphorylation of IRS-1 and activation of mTOR and p70S6K were attenuated by RE. RE restored the insulin-stimulated glucose uptake by enhancing GLUT4 glucose transporter translocation to plasma membrane.
Gluon dynamics from an ordinary differential equation
Authors: Aguilar A. C. , Ferreira M. N. , Papavassiliou J. 
Published: January 2021

AbstractWe present a novel method for computing the nonperturbative kinetic term of the gluon propagator from an ordinary differential equation, whose derivation hinges on the central hypothesis that the regular part of the three-gluon vertex and the aforementioned kinetic term are related by a partial Slavnov–Taylor identity. The main ingredients entering in the solution are projection of the three-gluon vertex and a particular derivative of the ghost-gluon kernel, whose approximate form is derived from a Schwinger–Dyson equation. Crucially, the requirement of a pole-free answer determines the initial condition, whose value is calculated from an integral containing the same ingredients as the solution itself. This feature fixes uniquely, at least in principle, the form of the kinetic term, once the ingredients have been accurately evaluated. In practice, however, due to substantial uncertainties in the computation of the necessary inputs, certain crucial components need be adjusted by hand, in order to obtain self-consistent results. Furthermore, if the gluon propagator has been independently accessed from the lattice, the solution for the kinetic term facilitates the extraction of the momentum-dependent effective gluon mass. The practical implementation of this method is carried out in detail, and the required approximations and theoretical assumptions are duly highlighted.
A warped scalar portal to fermionic dark matter
Authors: Carmona Adrian , Castellano Ruiz Javier , Neubert Matthias 
Published: January 2021

AbstractWe argue that extensions of the SM with a warped extra dimension, together with a new $${\mathbb {Z}}_2$$

Z
2

-odd scalar singlet, provide a natural explanation not only for the hierarchy problem but also for the nature of fermion bulk masses and the observed dark matter relic abundance. In particular, the Kaluza-Klein excitations of the new scalar particle, which is required to naturally obtain fermion bulk masses through Yukawa-like interactions, can be the leading portal to any fermion propagating into the bulk of the extra dimension and playing the role of dark matter. Moreover, such scalar excitations will necessarily mix with the Higgs boson, leading to modifications of the Higgs couplings and branching ratios, and allowing the Higgs to mediate the coannihilation of the fermionic dark matter. We study these effects and explore the viability of fermionic dark matter in the presence of these new heavy scalar mediators both in the usual freeze-out scenario and in the case where the freeze-out happens during an early period of matter domination.
$$U(1)_{B_3-L_2}$$ explanation of the neutral current $$B-$$anomalies
Authors: Allanach B. C. 
Published: January 2021

AbstractWe investigate a speculative short-distance force, proposed to explain discrepancies observed between measurements of certain neutral current decays of B hadrons and their Standard Model predictions. The force derives from a spontaneously broken, gauged $$U(1)_{B_3-L_2}$$

U

(
1
)

B
3

-

L
2

extension to the Standard Model, where the extra quantum numbers of Standard Model fields are given by third family baryon number minus second family lepton number. The only fields beyond those of the Standard Model are three right-handed neutrinos, a gauge field associated with $$U(1)_{B_3-L_2}$$

U

(
1
)

B
3

-

L
2

and a Standard Model singlet complex scalar which breaks $$U(1)_{B_3-L_2}$$

U

(
1
)

B
3

-

L
2

, a ‘flavon’. This simple model, via interactions involving a TeV scale force-carrying $$Z^\prime $$

Z
′

vector boson, can successfully explain the neutral current $$B-$$

B
-

anomalies whilst accommodating other empirical constraints. In an ansatz for fermion mixing, a combination of up-to-date $$B-$$

B
-

anomaly fits, LHC direct $$Z^\prime $$

Z
′

search limits and other bounds rule out the domain 0.15 $$\hbox {TeV}< M_{Z^\prime }<$$

TeV
<

M

Z
′

<

1.9 TeV at the $$95\%$$

95
%

confidence level. For more massive $$Z^\prime $$

Z
′

s, the model possesses a flavonstrahlung signal, where pp collisions produce a $$Z^\prime $$

Z
′

and a flavon, which subsequently decays into two Higgs bosons.
An improved E-payment protocol based on quantum blind signature without entanglement
Authors: Gou Xiang-Lin , Shi Run-Hua , Shi Ze , Li Kun-Chang 
Published: January 2021

E-payment plays an important role in modern daily life, so the security problem of E-payment has been widely concerned by researchers. In a recent paper [Int. J. Theor. Phys. 57, 2657 (2018)], the authors presented a trusted third-party E-payment protocol based on quantum blind signature without entanglement. In this paper, we show that there is a serious security flaw in their E-payment protocol. That is, the partial keys will be disclosed by performing a simple attack strategy. Furthermore, we propose an improved E-payment protocol and analyze its security.
Chapter 2.1a Ferrar Large Igneous Province: volcanology
Authors: Elliot David H. , White James D. L. , Fleming Thomas H. 
Published: January 2021

Abstract
Preserved rocks in the Jurassic Ferrar Large Igneous Province consist mainly of intrusions, and extrusive rocks, the topic of this chapter, comprise the remaining small component. They crop out in a limited number of areas in the Transantarctic Mountains and southeastern Australia. They consist of thick sequences of lavas and sporadic occurrences of volcaniclastic rocks. The latter occur mainly beneath the lavas and represent the initial eruptive activity, but also are present within the lava sequence. The majority are basaltic phreatomagmatic deposits and in at least two locations form immense phreatocauldrons filled with structureless tuff breccias and lapilli tuffs with thicknesses of as much as 400 m. Stratified sequences of tuff breccias, lapilli tuffs and tuffs are up to 200 m thick. Thin tuff beds are sparsely distributed in the lava sequences. Lava successions are mainly 400–500 m thick, and comprise individual lavas ranging from 1 to 230 m thick, although most are in the range of 10–100 m. Well-defined colonnade and entablature are seldom displayed. Lava sequences were confined topographically and locally ponded. Water played a prominent role in eruptive activity, as exhibited by phreatomagmatism, hyaloclastites, pillow lava and quenching of lavas. Vents for lavas have yet to be identified.
Chapter 2.2b Palmer Land and Graham Land volcanic groups (Antarctic Peninsula): petrology
Authors: Riley Teal R. , Leat Philip T. 
Published: January 2021

Abstract

Large-volume rhyolitic volcanism along the proto-Pacific margin of Gondwana consists of three major episodes of magmatism or ‘flare-ups’. The initial episode (V1) overlaps with the Karoo–Ferrar large igneous provinces at
c.
183 Ma. A second (V2) episode was erupted in the interval 171–167 Ma, and a third episode (V3) was emplaced in the interval 157–153 Ma. The magmatic events of the V1 and V2 episodes of the Antarctic Peninsula are reviewed here describing major and trace elements, and isotopic (Sr, Nd, O) data from rhyolitic volcanic rocks and more minor basaltic magmatism. An isotopically uniform intermediate magma developed as a result of anatexis of hydrous mafic lower crust, which can be linked to earlier, arc-related underplating. The subsequent lower-crust partial melts mixed with fractionated mafic underplate, followed by mid-crust storage and homogenization. Early Jurassic (V1) volcanic rocks of the southern Antarctic Peninsula are derived from the isotopically uniform magma, but they have mixed with melts of upper-crustal paragneiss in high-level magma chambers. The V2 rhyolites from the northern Antarctic Peninsula are the result of assimilation and fractional crystallization of the isotopically uniform magma. This process took place in upper-crust magma reservoirs involving crustal assimilants with an isotopic composition akin to that of the magma. A continental margin-arc setting was critical in allowing the development of an hydrous, fusible lower crust. Lower-crustal anatexis was in response to mafic underplating associated with the mantle plume thought to be responsible for the contemporaneous Karoo magmatic province and rifting associated with the initial break-up of Gondwana.
Reliability-aware Garbage Collection for Hybrid HBM-DRAM Memories
Authors: Liu Wenjie , Akram Shoaib , Sartor Jennifer B. , Eeckhout Lieven 
Published: January 2021

Emerging workloads in cloud and data center infrastructures demand high main memory bandwidth and capacity. Unfortunately, DRAM alone is unable to satisfy contemporary main memory demands. High-bandwidth memory (HBM) uses 3D die-stacking to deliver 4–8× higher bandwidth. HBM has two drawbacks: (1) capacity is low, and (2) soft error rate is high. Hybrid memory combines DRAM and HBM to promise low fault rates, high bandwidth, and high capacity. Prior OS approaches manage HBM by mapping pages to HBM versus DRAM based on hotness (access frequency) and risk (susceptibility to soft errors). Unfortunately, these approaches operate at a coarse-grained page granularity, and frequent page migrations hurt performance.
This article proposes a new class of reliability-aware garbage collectors for hybrid HBM-DRAM systems that place hot and low-risk objects in HBM and the rest in DRAM. Our analysis of nine real-world Java workloads shows that: (1) newly allocated objects in the nursery are frequently written, making them both hot and low-risk, (2) a small fraction of the mature objects are hot and low-risk, and (3) allocation site is a good predictor for hotness and risk. We propose RiskRelief, a novel reliability-aware garbage collector that uses allocation site prediction to place hot and low-risk objects in HBM. Allocation sites are profiled offline and RiskRelief uses heuristics to classify allocation sites as DRAM and HBM. The proposed heuristics expose Pareto-optimal trade-offs between soft error rate (SER) and execution time. RiskRelief improves SER by 9× compared to an HBM-Only system while at the same time improving performance by 29% compared to a DRAM-Only system. Compared to a state-of-the-art OS approach for reliability-aware data placement, RiskRelief eliminates all page migration overheads, which substantially improves performance while delivering similar SER. Reliability-aware garbage collection opens up a new opportunity to manage emerging HBM-DRAM memories at fine granularity while requiring no extra hardware support and leaving the programming model unchanged.
The Effectiveness of Acupuncture for Dysphagia after Stroke: A Systematic Review and Meta-Analysis
Authors: Zhong Lida , Wang Jing , Li Fang , Bao Xiao , Liu Huiyu , Wang Pu 
Published: January 2021

Objectives. This study reviewed and evaluated existing evidence of the efficacy of acupuncture as a clinical treatment for dysphagia after stroke. Methods. Five English and four Chinese databases were searched from inception to March 2020. All randomized controlled trials (RCTs) incorporating acupuncture or acupuncture combined with other interventions for the treatment of dysphagia after stroke were enrolled. All data were independently assessed and extracted by two authors. The bias risk assessment recommended by the Cochrane Collaboration's tool was used to assess the quality of the selected studies. This meta-analysis was conducted by using RevMan 5.3. Pooled analyses were calculated by the mean difference (MD) and 95% confidence interval (CI). Heterogeneity was assessed by the I2 test. Results. Thirty-five studies involving 3024 patients were analyzed. The meta-analysis showed that the therapeutic efficacy of acupuncture combined with other interventions was better than that of the control group for the standardized swallowing assessment (SSA) score (MD = −3.78, 95% CI: −4.64 to −2.91,

P
<
0.00001

), Ichiro Fujishima rating scale (IFRS) score (MD = 1.68, 95% CI: 1.16 to 2.20,

P
<
0.00001

), videofluoroscopic swallowing study (VFSS) score (MD = 2.26, 95% CI: 1.77 to 2.74,

P
<
0.00001

), and water swallowing test (WST) score (MD = −1.21, 95% CI: −1.85 to −0.57,

P
=

0.0002

). In studies reporting adverse effects, no serious outcome from an adverse event was confirmed. Conclusion. This systematic review indicated that acupuncture could be an effective therapy for treating dysphagia after stroke although stricter evaluation standards and rigorously designed RCTs are needed.
Assessing Lung Cancer Absolute Risk Trajectory Based on a Polygenic Risk Model
Authors: Hung Rayjean J. , Warkentin Matthew T. , Brhane Yonathan , Chatterjee Nilanjan , Christiani David C. , Landi Maria Teresa , Caporaso Neil E. , Liu Geoffrey , Johansson Mattias , Albanes Demetrius , Marchand Loic Le , Tardon Adonina , Rennert Gad , Bojesen Stig E. , Chen Chu , Field John K. , Kiemeney Lambertus A. , Lazarus Philip , Zienolddiny Shanbeth , Lam Stephen , Andrew Angeline S. , Arnold Susanne M. , Aldrich Melinda C. , Bickeböller Heike , Risch Angela , Schabath Matthew B. , McKay James D. , Brennan Paul , Amos Christopher I. 
Published: January 2021

Abstract

Lung cancer is the leading cause of cancer-related death globally. An improved risk stratification strategy can increase efficiency of low-dose CT (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. On the basis of 13,119 patients with lung cancer and 10,008 controls with European ancestry in the International Lung Cancer Consortium, we constructed a polygenic risk score (PRS) via 10-fold cross-validation with regularized penalized regression. The performance of risk model integrating PRS, including calibration and ability to discriminate, was assessed using UK Biobank data (N = 335,931). Absolute risk was estimated on the basis of age-specific lung cancer incidence and all-cause mortality as competing risk. To evaluate its potential clinical utility, the PRS distribution was simulated in the National Lung Screening Trial (N = 50,772 participants). The lung cancer ORs for individuals at the top decile of the PRS distribution versus those at bottom 10% was 2.39 [95% confidence interval (CI) = 1.92–3.00; P = 1.80 × 10−14] in the validation set (Ptrend = 5.26 × 10−20). The OR per SD of PRS increase was 1.26 (95% CI = 1.20–1.32; P = 9.69 × 10−23) for overall lung cancer risk in the validation set. When considering absolute risks, individuals at different PRS deciles showed differential trajectories of 5-year and cumulative absolute risk. The age reaching the LDCT screening recommendation threshold can vary by 4 to 8 years, depending on the individual's genetic background, smoking status, and family history. Collectively, these results suggest that individual's genetic background may inform the optimal lung cancer LDCT screening strategy.

Significance:
Three large-scale datasets reveal that, after accounting for risk factors, an individual's genetics can affect their lung cancer risk trajectory, thus may inform the optimal timing for LDCT screening.