bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Protective Effect of Neuromuscular Training on the Medial Tibial Stress Syndrome in Youth Female Track-and-Field Athletes: A Clinical Trial and Cohort Study
Authors: Mendez-Rebolledo Guillermo , Figueroa-Ureta Romina , Moya-Mura Fernanda , Guzmán-Muñoz Eduardo , Ramirez-Campillo Rodrigo , Lloyd Rhodri S. 
Published: April 2021

Context: Few reports have analyzed the effects of neuromuscular (NM) training programs on the injury incidence among youth female track-and-field athletes. Objective: To determine the effects of NM training on reducing lower limb injury incidence and to establish its effects on countermovement jump performance, balance, 30-m sprint, and joint position sense in youth female track-and-field athletes. Design: Single-blind, randomized controlled clinical trial. Setting: Sports research laboratory. Participants: Twenty-two female athletes were allocated into 2 groups: Conventional (CONV) training (n = 11; age = 15.3 [2.1] y) and NM training (n = 11; age = 15.0 [2.7] y). Interventions: Interventions were performed during the preseason of 6 weeks. The CONV training included anaerobic, strength, and aerobic training. The NM training consisted of a multicomponent program that integrated jumps, landings, and running with strength, endurance, agility, balance, and CORE training. Main Outcome Measures: A follow-up of the cohorts was carried out through the evaluation of lower limb injuries (main outcome) during a regular season (weeks 7–18). Secondary outcomes were measured before and after the intervention: Y-balance test, active joint repositioning, ground reaction force, and countermovement jump height. Results: The injury incidence rate was 17.89 injuries per 1000 hours athlete-exposure in CONV training, and 6.58 in NM training (relative risk = 0.38; 95% confidence interval, 0.18 to 0.82; P = .044). Particularly, the medial tibial stress syndrome incidence rate was 5.96 injuries per 1000 hours athlete-exposure in CONV training and 0.82 in NM training (relative risk = 0.17; 95% confidence interval, 0.02 to 1.12; P = .012). In addition, a significant training × time interaction was noted, favoring improvements in 30-m sprint and countermovement jump height after NM. Conclusion: The NM training may improve youth female athlete’s physical fitness and reduce their injury relative risk of medial tibial stress syndrome injury.
Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma
Authors: Beasley Georgia M , Nair Smita K , Farrow Norma E , Landa Karenia , Selim Maria Angelica , Wiggs Carol Ann , Jung Sin-Ho , Bigner Darell D , True Kelly Andrea , Gromeier Matthias , Salama April KS 
Published: April 2021

BackgroundWhile programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation.MethodsAn open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections.ResultsPVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months.ConclusionIntratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients.Trial registration numberNCT03712358
Cardiovascular risk factors and autonomic indices in relation to fatal and non-fatal coronary events
Authors: Zambach Christian , Fedorowski Artur , Borné Yan , Johnson Linda S B , Gerward Sofia , Hamrefors Viktor , Engström Gunnar 
Published: April 2021

ObjectiveMortality caused by coronary artery disease has markedly decreased in recent years. However, a substantial proportion of patients suffering a coronary event (CE) die within the first day, most of them out of hospital. We aimed to investigate how established cardiovascular (CV) risk factors and CV autonomic indices associate with fatal versus non-fatal CEs in the population.Methods33 057 individuals (mean age; 45.6 years; 10 773 women) free of coronary artery disease at baseline were included. Baseline examination, including assessment of traditional CV risk factors and autonomic indices such as heart rate and orthostatic reaction, was performed during 1974–1992, after which the subjects were monitored for incident CV disease. The Lunn-McNeil competing risks approach with a prespecified multivariable model was used to assess differences in risks for fatal and non-fatal CEs in relation to baseline CV risk factors.ResultsDuring follow-up period of 29.7 years, 5494 subjects (6.10/1000 person-years) had first CE; 1554 of these were fatal. Age, male gender, smoking, body mass index (BMI), blood pressure, pulse pressure and resting heart rate had stronger relationships with fatal CE than with non-fatal events. The effects of diabetes, serum cholesterol, antihypertensive treatment and orthostatic blood pressure responses were similar for fatal and non-fatal CE.ConclusionsSeveral cardiovascular risk factors, such as smoking, high BMI, blood pressure and high resting heart rate, were preferentially associated with fatal compared with non-fatal CEs. These observations may require special attention in the overall efforts to further reduce coronary artery disease mortality.
Evaluation of latest viscoelastic coagulation assays in the transcatheter aortic valve implantation setting
Authors: Fanning Jonathon , Roberts Shaun , Merza Megan , Anstey Chris , Poon Karl , Incani Alexander , Natani Sarvesh , Fraser John 
Published: April 2021

BackgroundPoint of care viscoelastic measures with thromboelastography (TEG; Haemonetics Corporation, Switzerland) and thromboelastometry (ROTEM, Tem Innovations GmbH, Germany) now supersede laboratory assays in the perioperative assessment and management of coagulation. To the best of our knowledge, this sophisticated coagulation assessment has not been performed to characterise thrombotic changes in the transcatheter aortic valve implantation (TAVI) setting, nor have the two latest iteration cartridge-based systems been directly compared in the elective perioperative period.MethodsPatients undergoing TAVI were prospectively recruited. Samples (n=44) were obtained at four timepoints (postinduction of anaesthesia, postheparin (100 IU/kg), postprotamine (1 mg/100 IU heparin) and 6 hours postoperatively). Each sample was concurrently assessed with standard laboratory tests (prothrombin time/international normalised ratio, activated partial thromboplastin time, thrombin clotting time, platelet count and direct fibrinogen, ROTEMSigma and TEG6s).ResultsClot strength showed a statistically significant increase postheparin/TAVI deployment. When considering the subgroup of samples taken following the administration heparin, the heparinase channel of the TEG6s did not yield clotting strength results in 55% of samples and clotting time exceeded the upper limit of normal in 70% of samples. It was retrospectively recognised that the arachidonic acid channel of the TEG6s Platelet Mapping Cartridge had been decommissioned prohibiting assessment of aspirin effect.ConclusionsThis study demonstrated a small intraprocedural prothrombotic change of uncertain clinical importance during the transcatheter aortic valve procedure. Further comparison with percutaneous coronary intervention and aortic valve replacement cohorts are needed to assess the merits of current antithrombotic guidelines, which are extrapolated from the PCI setting. The heparin effect was more consistently quantified by ROTEM.
Evaluation and modeling of factors influencing the depth of mixing layer in which soil solute releasing from soil to surface runoff
Authors: Zhou Beibei , Chen Xiaopeng , Su Lijun , Li Hujun , Wang Quanjiu , Tao Wanghai 
Published: April 2021

The depth of mixing layer is one of the important parameters which cannot be assigned a constant value affected by many factors in the slope runoff. The objective of this study was to investigate the effect of slope length and underground biomass on slope runoff, solute transport processes, as well as mixing layer depth. In this study, the experimental plots with the four slope lengths (5, 10, 15, and 20 m) and a width of 2 m were built on the slope with the gradient of 20°. In addition, the plots with the millet or wheat planting were built on the slope. The change of runoff and solute transport was analyzed through simulated rainfall experiments and then to estimate mixing layer depth. The results showed that the runoff rate decreased and more runoff seeped into the slope soil with increasing slope length. Increasing underground biomass also promoted greater rainfall infiltration into the soil. The increase in slope length increased the concentration of solute in runoff, but more underground biomass reduced the nutrients transported with runoff. The effective mixing depth increased with an increase in slope length, but effective mixing depth decreased with increased underground biomass. The modified expression of the equivalent mixing model under different slope lengths and underground biomass could accurately describe the solute transfer process in runoff when compared with complete mixing model and incomplete mixing model based on exponential functions. This research provided a reference for improving the application of mixing layer models in the slope management.
Magnetic dominance of axion electrodynamics: photon capture effect and anisotropy of Coulomb potential
Authors: Villalba-Chávez S. , Shabad A. E. , Müller C. 
Published: April 2021

AbstractFor magnetic fields larger than the characteristic scale linked to axion-electrodynamics, quantum vacuum fluctuations due to axion-like fields can dominate over those associated with the electron-positron fields. This conjecture is explored by investigating both the axion-modified photon capture by a strong magnetic field and the Coulomb potential of a static pointlike charge. We show that in magnetic fields characteristic of neutron stars$$\sim 10^{13}$$∼1013–$$10^{15}\;\mathrm{G}$$1015G, the capture of gamma photons prior to the production of a pair can prevent the existence of an electron-positron plasma, essential for explaining the pulsar radiation mechanism. This incompatibility is used to limit the axion parameter space. Our bounds improve existing outcomes in the region of mass$$m\sim 10^{-10}$$m∼10-10–$$10^{-5}\;{\mathrm{eV}}$$10-5eV. The effect of capture, known in QED as relating to gamma-quanta, is extended in axion electrodynamics to include X-ray photons with the result that a specially polarized part of the heat radiation from the surface is canalized along the magnetic field. Besides, we find that in the regime in which the dominance takes place, the running QED coupling depends on the field strength and the modified Coulomb potential is of Yukawa-type in the direction perpendicular to the magnetic field at distances much smaller than the axion Compton wavelength, while along the field it follows approximately the Coulomb law at any length scale. Despite the Coulomb singularity manifested in the latter case, we argue that the ground-state energy of a non-relativistic hydrogen atom placed in a strong magnetic field turns out to be bounded due to the nonrenormalizable feature of axion-electrodynamics.
FINE-GRAINED AND MULTI-SCALE MOTIF FEATURES FOR CROSS-SUBJECT MENTAL WORKLOAD ASSESSMENT USING BI-LSTM
Authors: SHAO SHILIANG , WANG TING , SONG CHUNHE , SU YUN , WANG YONGLIANG , YAO CHEN 
Published: April 2021

Mental workload (MW) assessment is crucial for understanding human mental state. Cross-subject MW analysis based on electroencephalogram (EEG) signals is an important way. In this paper, a fine-grained and multi-scale motif (FGMSM) features extraction method is proposed, and the proposed features together with original EEG data are used as the input of bidirectional long short-term memory (Bi-LSTM) to evaluate the cross-subject mental workload. First, the EEG signal of each channel is decomposed based on improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) algorithm. Second, for the motif structure consisting of three nodes, multi-scale detection is carried out in each intrinsic mode function, and the proportion of each motif structure is extracted as the newly extracted features. Then, the statistical differences of the extracted features between different MW levels are analyzed by using the [Formula: see text]-test, and the features with statistical differences are selected for the cross-subject MW assessment. Finally, based on the public dataset with 26 subjects, Bi-LSTM and a variety of machine learning algorithms are used to classify the levels of cross-subject MW. The results show that the Bi-LSTM classification method with the original EEG data and the proposed features show the most positive results. Therefore, the FGMSM features proposed in this paper with Bi-LSTM provide a new technique for the assessment of cross-subject MW based on EEG signals.
Parameterized Approximation Algorithms for Bidirected Steiner Network Problems
Authors: Chitnis Rajesh , Feldmann Andreas Emil , Manurangsi Pasin 
Published: April 2021

The D
irected
S
teiner
N
etwork
(DSN) problem takes as input a directed graph
G
=(
V
,
E
) with non-negative edge-weights and a set
D
⊆
V
×
V
of
k
demand pairs. The aim is to compute the cheapest network
N⊆ G
for which there is an
s\rightarrow t
path for each (
s
,
t
)∈ D. It is known that this problem is notoriously hard, as there is no
k

1/4−
o
(1)

-approximation algorithm under Gap-ETH, even when parametrizing the runtime by
k
[Dinur & Manurangsi, ITCS 2018]. In light of this, we systematically study several special cases of DSN and determine their parameterized approximability for the parameter
k
.

For the
bi
-DSNP
lanar
problem, the aim is to compute a solution
N⊆ G
whose cost is at most that of an optimum planar solution in a bidirected graph
G
, i.e., for every edge
uv
of
G
the reverse edge
vu
exists and has the same weight. This problem is a generalization of several well-studied special cases. Our main result is that this problem admits a parameterized approximation scheme (PAS) for
k
. We also prove that our result is tight in the sense that (a) the runtime of our PAS cannot be significantly improved, and (b) no PAS exists for any generalization of bi-DSNP
lanar
, under standard complexity assumptions. The techniques we use also imply a polynomial-sized approximate kernelization scheme (PSAKS). Additionally, we study several generalizations of
bi
-DSNP
lanar
and obtain upper and lower bounds on obtainable runtimes parameterized by
k
.

One important special case of DSN is the S
trongly
C
onnected
S
teiner
S
ubgraph
(SCSS) problem, for which the solution network
N⊆ G
needs to strongly connect a given set of
k
terminals. It has been observed before that for SCSS a parameterized 2-approximation exists for parameter
k
[Chitnis et al., IPEC 2013]. We give a tight inapproximability result by showing that for
k
no parameterized (2 − ε)-approximation algorithm exists under Gap-ETH. Additionally, we show that when restricting the input of SCSS to bidirected graphs, the problem remains NP-hard but becomes FPT for
k
.
Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer
Authors: Kazi Aslamuzzaman , Chen Liwei , Xiang Shengyan , Vangipurapu Rajanikanth , Yang Hua , Beato Francisca , Fang Bin , Williams Terence M. , Husain Kazim , Underwood Patrick , Fleming Jason B. , Malafa Mokenge , Welsh Eric A. , Koomen John , Trevino José , Sebti Saïd M. 
Published: April 2021

Abstract

Purpose:
Among human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency.

Experimental Design:
Global phosphoproteomics, screening of a chemical library of FDA drugs, and genome-wide CRISPR/Cas9 viability database analysis were used to identify vulnerabilities of KRas dependency.

Results:
Global phosphoproteomics revealed that KRas dependency is driven by a cyclin-dependent kinase (CDK) network. CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as knocking out KRas. Furthermore, screening of a library of FDA drugs identified AT7519, a CDK1, 2, 7, and 9 inhibitor, as a potent inducer of apoptosis in mt KRas-dependent, but not in mt KRas-independent, human cancer cells. In vivo AT7519 inhibited the phosphorylation of CDK1, 2, 7, and 9 substrates and suppressed growth of xenografts from 5 patients with pancreatic cancer. AT7519 also abrogated mt KRas and mt p53 primary and metastatic pancreatic cancer in three-dimensional (3D) organoids from 2 patients, 3D cocultures from 8 patients, and mouse 3D organoids from pancreatic intraepithelial neoplasia, primary, and metastatic tumors.

Conclusions:
A link between CDK hyperactivation and mt KRas dependency was uncovered and pharmacologically exploited to abrogate mt KRas-driven pancreatic cancer in highly relevant models, warranting clinical investigations of AT7519 in patients with pancreatic cancer.
Durvalumab Combined with Immunomodulatory Drugs (IMiD) Overcomes Suppression of Antitumor Responses due to IMiD-induced PD-L1 Upregulation on Myeloma Cells
Authors: Ishibashi Mariko , Yamamoto Junichi , Ito Takumi , Handa Hiroshi , Sunakawa-Kii Mika , Inokuchi Koiti , Morita Rimpei , Tamura Hideto 
Published: April 2021

Abstract
We previously showed that the interaction of programmed death-ligand 1 (PD-L1) on multiple myeloma (MM) cells with PD-1 not only inhibits tumor-specific cytotoxic T-lymphocyte activity via the PD-1 signaling pathway but also induces drug resistance via PD-L1–mediated reverse signals. We here examined the regulation of PD-L1 expression by immunomodulatory drugs (IMiDs) and antimyeloma effects of the anti–PD-L1 antibody durvalumab in combination with IMiDs. IMiDs induced PD-L1 expression on IMiD-insensitive MM cells and plasma cells from patients newly diagnosed with MM. Gene-expression profiling analysis demonstrated that not only PD-L1, but also a proliferation-inducing ligand (APRIL), was enhanced by IMiDs. PD-L1 induction by IMiDs was suppressed by using the APRIL inhibitor recombinant B-cell maturation antigen (BCMA)-Ig, the antibody against BCMA, or an MEK/ERK inhibitor in in vitro and in vivo assays. In addition, its induction was abrogated in cereblon (CRBN)-knockdown MM cells, whereas PD-L1 expression was increased and strongly induced by IMiDs in Ikaros-knockdown cells. These results demonstrated that PD-L1 upregulation by IMiDs on IMiD-insensitive MM cells was induced by (i) the BCMA–APRIL pathway via IMiD-mediated induction of APRIL and (ii) Ikaros degradation mediated by CRBN, which plays a role in inhibiting PD-L1 expression. Furthermore, T-cell inhibition induced by PD-L1–upregulated cells was effectively recovered after combination treatment with durvalumab and IMiDs. PD-L1 upregulation by IMiDs on MM cells might promote aggressive myeloma behaviors and immune escape in the bone marrow microenvironment.
Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas
Authors: Zheng Tuyu , Ghasemi David R. , Okonechnikov Konstantin , Korshunov Andrey , Sill Martin , Maass Kendra K. , Benites Goncalves da Silva Patricia , Ryzhova Marina , Gojo Johannes , Stichel Damian , Arabzade Amir , Kupp Robert , Benzel Julia , Taya Shinichiro , Adachi Toma , Shiraishi Ryo , Gerber Nicolas U. , Sturm Dominik , Ecker Jonas , Sievers Philipp , Selt Florian , Chapman Rebecca , Haberler Christine , Figarella-Branger Dominique , Reifenberger Guido , Fleischhack Gudrun , Rutkowski Stefan , Donson Andrew M. , Ramaswamy Vijay , Capper David , Ellison David W. , Herold-Mende Christel C. , Schüller Ulrich , Brandner Sebastian , Driever Pablo Hernáiz , Kros Johan M. , Snuderl Matija , Milde Till , Grundy Richard G. , Hoshino Mikio , Mack Stephen C. , Gilbertson Richard J. , Jones David T.W. , Kool Marcel , von Deimling Andreas , Pfister Stefan M. , Sahm Felix , Kawauchi Daisuke , Pajtler Kristian W. 
Published: April 2021

Abstract

Molecular groups of supratentorial ependymomas comprise tumors with ZFTA–RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally supratentorial ependymomas cannot be readily assigned to any of these groups due to lack of detection of a typical fusion and/or ambiguous DNA methylation–based classification. An unbiased approach with a cohort of unprecedented size revealed distinct methylation clusters composed of tumors with ependymal but also various other histologic features containing alternative translocations that shared ZFTA as a partner gene. Somatic overexpression of ZFTA-associated fusion genes in the developing cerebral cortex is capable of inducing tumor formation in vivo, and cross-species comparative analyses identified GLI2 as a key downstream regulator of tumorigenesis in all tumors. Targeting GLI2 with arsenic trioxide caused extended survival of tumor-bearing animals, indicating a potential therapeutic vulnerability in ZFTA fusion–positive tumors.

Significance:
ZFTA–RELA fusions are a hallmark feature of supratentorial ependymoma. We find that ZFTA acts as a partner for alternative transcriptional activators in oncogenic fusions of supratentorial tumors with various histologic characteristics. Establishing representative mouse models, we identify potential therapeutic targets shared by ZFTA fusion–positive tumors, such as GLI2.
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