bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of first pass reperfusion on outcome in patients with posterior circulation ischemic stroke
Authors: den Hartog Sanne J , Roozenbeek Bob , Boodt Nikki , Bruggeman Agnetha A E , van Es Adriaan C G M , Emmer Bart J , Majoie Charles B L M , van den Wijngaard Ido R , van Doormaal Pieter Jan , van Zwam Wim H , Lingsma Hester F , Dippel Diederik W J 
Published: May 2021

BackgroundFirst pass reperfusion (FPR), that is, excellent reperfusion (expanded treatment in cerebral ischemia (eTICI) 2C-3) in one pass, after endovascular treatment (EVT) of an occluded artery in the anterior circulation, is associated with favorable clinical outcome, even when compared with multiple pass excellent reperfusion (MPR). In patients with posterior circulation ischemic stroke (PCS), the same association is expected, but currently unknown. We aimed to assess characteristics associated with FPR and the influence of FPR versus MPR on outcomes in patients with PCS.MethodsWe used data from the MR CLEAN Registry, a prospective observational study. The effect of FPR on 24-hour National Institutes of Health Stroke Scale (NIHSS) score, as percentage reduction, and on modified Rankin Scale (mRS) scores at 3 months, was tested with linear and ordinal logistic regression models.ResultsOf 224 patients with PCS, 45 patients had FPR, 47 had MPR, and 90 had no excellent reperfusion (eTICI <2C). We did not find an association between any of the patient, imaging, or treatment characteristics and FPR. FPR was associated with better NIHSS (−45% (95% CI: −65% to −12%)) and better mRS scores (adjusted common odds ratio (acOR): 2.16 (95% CI: 1.23 to 3.79)) compared with no FPR. Outcomes after FPR were also more favorable compared with MPR, but the effect was smaller and not statistically significant (NIHSS: −14% (95% CI: −51% to 49%), mRS acOR: 1.50 (95% CI: 0.75 to 3.00)).ConclusionsFPR in patients with PCS is associated with favorable clinical outcome in comparison with no FPR. In comparison with MPR, the effect of FPR was no longer statistically significant. Nevertheless, our data support the notion that FPR should be the treatment target to pursue in every patient treated with EVT.
Predilection for physical activity and body mass index z-score can quickly identify children needing support for a physically active lifestyle
Authors: Longmuir Patricia E. , Prikryl Emil , Rotz Heather L.L. , Boyer Charles , Alpous Anastasia 
Published: May 2021

Comprehensive physical literacy assessments can be time-consuming and require a gymnasium space and examiner training. This project sought to identify easy-to-administer tasks, suitable for all physical activity and healthcare settings, which could quickly screen a group of children to identify those most likely to benefit from an in-depth assessment or additional physical literacy support. The 40 potential screening tasks were compared with the Canadian Assessment of Physical Literacy among 226 children (57% female) aged 8 to 12 years. Absolute body mass index z-score above 0.67 or predilection for physical activity less than 31.5/36 points had the highest sensitivity (81% and 83%, respectively) and specificity (45% and 52%, respectively). Predilection less than 31.5 combined with absolute body mass index z-scores achieved 81% sensitivity and 64% sensitivity. When the selected tasks were repeated on a different sample of 71 children (50% female), results were similar with the combination of predilection and absolute body mass index achieving 92% sensitivity and 53% specificity. Predilection for physical activity, absolute body mass index z-score, and a combination of the two are quick and easy screening tasks suitable for all physical activity settings that can identify children likely to need additional support for a physically active lifestyle. Novelty: Physical literacy screening can be completed in recreation, education, allied health, coaching and healthcare settings. Predilection for physical activity and body mass index z-score quickly identify children needing physical literacy support.
Effects of red-osier dogwood extracts on growth performance, intestinal digestive and absorptive functions, and meat quality of broiler chickens
Authors: Mogire Marion K. , Choi Janghan , Lu Peng , Yang Chongwu , Liu Shangxi , Adewole Deborah , Rodas-Gonzalez Argenis , Yang Chengbo 
Published: May 2021

A total of 320 one-day-old Cobb 500 chicks with an initial weight of 48.3 ± 3.3 g·pen−1 were assigned to four dietary treatments with eight replicates provided in three phases for 46 d. The treatments were fed as mash diets and included (1) negative control (NC) corn-soybean basal diet, (2) positive control (PC) basal diet with 30 ppm avilamycin, (3) basal diet supplemented with 1000 ppm red-osier dogwood extracts (RDE1), and (4) basal diet with 3000 ppm red-osier dogwood extracts (RDE2). Results showed reduced jejunal crypt depth in RDE1 and increased villus:crypt ratio in groups (either RDE1 or RDE2) (P < 0.05). Cationic amino acid (AA) transporter mRNA abundance was decreased (P < 0.05) in RDE1, RDE2, and PC treatments, but peptide and neutral AA transporter mRNA abundance were higher (P < 0.05) in RDE2 compared with NC. Apparent ileal digestibility of crude fat was increased in RDE2 and PC compared with NC, whereas AA digestibility was greater in RDE1, RDE2, and PC (P < 0.05). In conclusion, red-osier dogwood had no effect on growth performance, improved the intestinal health and function of broiler chickens, and had no detrimental effects on meat quality.
On the photon-pseudoscalar particle mixing in media and external fields
Authors: Ejlli Damian 
Published: May 2021

AbstractIn this work, I study the mixing of photons with pseudoscalar particles and vice-versa in the presence of an external magnetic field and a pseudoscalar field. I solve exactly for the first time in the literature the equations of motion of the electromagnetic field coupled with a pseudoscalar field in the presence of a constant magnetic field with arbitrary direction with respect to the direction of propagation of the fields in vacuum. In addition, I also solve exactly the equations of motion in a magnetized plasma/gas for perpendicular propagation with respect to the external magnetic field. By finding exact solutions to the equations of motion, I find exact expressions for the transition efficiencies of photons into pseudoscalar particles in different situations. The expressions of the transition efficiencies generalize and correct those previously found in the literature by using approximate WKB methods on solving the equations of motion. In the case when the direction of propagation of fields with respect to the external magnetic field is not perpendicular, a longitudinal state of the electromagnetic field is generated even in a magnetized vacuum. The appearance of the longitudinal electric field state could be used for laboratory searches of pseudoscalar particles such as the axion and/or axion-like particles.
Masking singularities in Weyl gravity and Ricci flows
Authors: Dzhunushaliev Vladimir , Folomeev Vladimir 
Published: May 2021

AbstractWithin vacuum Weyl gravity, we obtain a solution by which, using different choices of the conformal factor, we derive metrics describing (i) a bounce of the universe; (ii) toroidal and spherical wormholes; and (iii) a change in metric signature. It is demonstrated that singularities occurring in these systems are “masked”. We give a simple explanation of the possibility of masking the singularities within Weyl gravity. It is shown that in the first and third cases the three-dimensional metrics form Ricci flows. The question of the possible applicability of conformal Weyl gravity as some phenomenological theory in an approximate description of quantum gravity is discussed.
Nitrate transport in the chalk vadose zone in Picardy, France
Authors: Surdyk Nicolas , Gourcy Laurence , Bault Violaine , Baran Nicole 
Published: May 2021

Abstract
Since the 1980s, nitrate has been shown to be present in soils and the vadose zone of various types of geological materials years after fertilizer application. In chalk, where the vadose zone is thick, nitrate storage can be considerable and its transport time towards groundwater can be lengthy. In this context, evaluation of the impact of changes in agricultural practices on groundwater quality remains a major question. Improvement of groundwater quality can in certain cases be greatly delayed after the implementation of environmental agricultural practices.

The principal objective of this study is to improve our knowledge of when changes in agricultural practices will have a noticeable effect on groundwater quality. To meet this objective, nitrate concentration profiles were performed in agricultural plots in Picardy (France). A crop marker event was used to calculate the transport velocity of water and associated solutes. This method is useful when other tracers (such as tritium or chloride) cannot be used. Estimated velocities range from 0.51 to 0.54 m a
−1
; these values are similar to those described in similar chalk aquifers.
Advances in conceptualizing transport in chalk aquifers
Authors: Foley Aidan E. , Worthington Stephen R. H. 
Published: May 2021

Abstract
The conceptualizations of matrix, fracture and fissure porosity are important for understanding relative controls on storage and flow of groundwater, and the transport of solutes (and non-aqueous phase liquids) within chalk aquifers. However, these different types of porosity, rather than being entirely distinct, represent elements in a continuum of void sizes contributing to the total porosity of the aquifer. Here we define such a continuum and critically examine the selection of appropriate values of effective porosity, a widely used parameter for mass transport modelling in aquifers. Effective porosity is a transient phenomenon, related to the porosity continuum by the timescales under which mass transport occurs. An analysis of 55 tracer tests and 20 well inflow tests in English Chalk aquifers identifies spatial scaling in groundwater velocity and groundwater flow respectively, which are interpreted within the context of the wider literature on carbonate aquifers globally. We advance transport modelling in the Chalk by developing a fissure aperture velocity mapping method using transmissivity data from existing regional groundwater models, together with the identified transient and spatial scaling phenomena. The results show that chalk aquifers exhibit widespread rapid groundwater flow which may transport contaminants rapidly in almost any setting.
Development of spatial permeability variations in English Chalk aquifers
Authors: Worthington Stephen R. H. , Foley Aidan E. 
Published: May 2021

Abstract
The Cretaceous Chalk in England forms dual-porosity aquifers, with low-permeability matrix and high-permeability networks of fissures, which are predominantly stress-relief fractures that have been enlarged by dissolution. This enlargement is a function of the volume of water that has passed along a fracture (the flowrate effect) and its degree of chemical undersaturation. Feedback effects result in the development of a distinctive permeability structure, with four particular characteristics: (i) troughs in the water table with high transmissivity and convergent groundwater flow; (ii) substantial increases in transmissivities in a downgradient direction; (iii) downgradient decreases in hydraulic gradient; and (iv) discharge from the high-transmissivity zones to the surface commonly at substantial springs. This distinctive self-organized permeability structure occurs throughout unconfined chalk aquifers. Early enlargement of fissures at a depth of 50–100 m below the water table is slow, but is much more rapid close to the water table and in the uppermost bedrock due to non-linear dissolution kinetics. A modelled dissolution profile shows that more than 95% of dissolution takes place in the top 1 m of bedrock, and that enlargement of fissures in the saturated zone results from progressive dissolution occurring over a period of a million years or more.
Phase I–II Open-Label Multicenter Study of Palbociclib + Vemurafenib in BRAFV600MUT Metastatic Melanoma Patients: Uncovering CHEK2 as a Major Response Mechanism
Authors: Louveau Baptiste , Resche-Rigon Matthieu , Lesimple Thierry , Da Meda Laetitia , Pracht Marc , Baroudjian Barouyr , Delyon Julie , Amini-Adle Mona , Dutriaux Caroline , Reger de Moura Coralie , Sadoux Aurélie , Jouenne Fanélie , Ghrieb Zineb , Vilquin Paul , Bouton Didier , Tibi Annick , Huguet Samuel , Rezai Keyvan , Battistella Maxime , Mourah Samia , Lebbe Céleste 
Published: May 2021

Abstract

Purpose:
In BRAFV600MUT metastatic melanoma, cyclin D–CDK4/6–INK4–Rb pathway alterations are involved in resistance to MAPK inhibitors, suggesting a clinical benefit of cyclin-dependent kinase 4 (CDK4) inhibitors. In this phase I–II study, we aimed to establish the MTD of palbociclib when added to vemurafenib.

Patients and Methods:
Patients with BRAFV600E/KMUT metastatic melanoma harboring CDKN2A loss and RB1 expression were included and stratified into two groups according to previous BRAF inhibitor treatment (no:strata 1; yes:strata 2). Treatment comprised palbociclib once daily for 14 days followed by a 7-day break + continuous dosing of vemurafenib. The primary endpoint was the occurrence of dose-limiting toxicity (DLT), and the secondary endpoints included the best response, survival, pharmacokinetics, and tumor molecular profiling.

Results:
Eighteen patients were enrolled, with 15 in strata 2. Characteristics at inclusion were American Joint Committee on Cancer stage IVM1c (N = 16; 88.9%), high lactate dehydrogenase (N = 9; 50.0%), and median number of previous treatments of 2. One and 5 patients experienced DLT in strata 1 and 2, respectively, defining the MTD at palbociclib 25 mg and vemurafenib 960 mg in strata 2. No significant evidence for drug–drug interactions was highlighted. The median progression-free survival was 2.8 months, and 5 (27.8%) patients showed a clinical response. The baseline differential mRNA expression analysis and in vitro data revealed the role of CHEK2 in the response to palbociclib.

Conclusions:
Although the combination of palbociclib + fixed-dose vemurafenib did not allow an increased palbociclib dosage above 25 mg, a significant clinical benefit was achieved in pretreated patients with melanoma. An association between the transcriptomic data and clinical response was highlighted.
Deep Learning for Fully Automated Prediction of Overall Survival in Patients with Oropharyngeal Cancer Using FDG-PET Imaging
Authors: Cheng Nai-Ming , Yao Jiawen , Cai Jinzheng , Ye Xianghua , Zhao Shilin , Zhao Kui , Zhou Wenlan , Nogues Isabella , Huo Yuankai , Liao Chun-Ta , Wang Hung-Ming , Lin Chien-Yu , Lee Li-Yu , Xiao Jing , Lu Le , Zhang Ling , Yen Tzu-Chen 
Published: May 2021

AbstractPurpose:Accurate prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is crucial. We developed an objective and robust deep learning–based fully-automated tool called the DeepPET-OPSCC biomarker for predicting overall survival (OS) in OPSCC using [18F]fluorodeoxyglucose (FDG)-PET imaging.Experimental Design:The DeepPET-OPSCC prediction model was built and tested internally on a discovery cohort (n = 268) by integrating five convolutional neural network models for volumetric segmentation and ten models for OS prognostication. Two external test cohorts were enrolled—the first based on the Cancer Imaging Archive (TCIA) database (n = 353) and the second being a clinical deployment cohort (n = 31)—to assess the DeepPET-OPSCC performance and goodness of fit.Results:After adjustment for potential confounders, DeepPET-OPSCC was found to be an independent predictor of OS in both discovery and TCIA test cohorts [HR = 2.07; 95% confidence interval (CI), 1.31–3.28 and HR = 2.39; 95% CI, 1.38–4.16; both P = 0.002]. The tool also revealed good predictive performance, with a c-index of 0.707 (95% CI, 0.658–0.757) in the discovery cohort, 0.689 (95% CI, 0.621–0.757) in the TCIA test cohort, and 0.787 (95% CI, 0.675–0.899) in the clinical deployment test cohort; the average time taken was 2 minutes for calculation per exam. The integrated nomogram of DeepPET-OPSCC and clinical risk factors significantly outperformed the clinical model [AUC at 5 years: 0.801 (95% CI, 0.727–0.874) vs. 0.749 (95% CI, 0.649–0.842); P = 0.031] in the TCIA test cohort.Conclusions:DeepPET-OPSCC achieved an accurate OS prediction in patients with OPSCC and enabled an objective, unbiased, and rapid assessment for OPSCC prognostication.
Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors
Authors: Tsimberidou Apostolia M. , Beer Philip A. , Cartwright Carrie A. , Haymaker Cara , Vo Henry H. , Kiany Simin , Cecil Alexander R.L. , Dow James , Haque Kemal , Silva Franck A. , Coe Lucy , Berryman Helen , Bone Elisabeth A. , Nogueras-Gonzalez Graciela M. , Vining David , McElwaine-Johnn Hilary , Wistuba Ignacio I. 
Published: May 2021

Abstract

Purpose:
Inhibition of histone deacetylase 6 (HDAC6) is predicted to deliver both direct antitumor activity and modulation of the antitumor immune response. This study describes the development of a novel HDAC6 inhibitor.

Patients and Methods:
KA2507 was characterized in HDAC biochemical and cellular target engagement assays and in preclinical efficacy models of melanoma and colorectal cancer. In a phase I study, KA2507 was administered orally using a 3+3 dose-escalation design (NCT03008018).

Results:
KA2507 is a potent and selective inhibitor of HDAC6 (biochemical IC50 = 2.5 nmol/L). Preclinical models demonstrated antitumor efficacy in syngeneic tumor-bearing mice, with translational studies highlighting modulation of the antitumor immune response. Twenty patients were treated in a phase I study. KA2507 was well tolerated; dose-limiting toxicity was not observed up to the maximum dose administered. Pharmacokinetic profiling supported twice-daily oral dosing. Pharmacodynamic analysis demonstrated selective HDAC6 target engagement in peripheral blood cells, free from off-target class I HDAC activity. Stable disease was the best clinical response (7 patients). Three of these patients (adenoid cystic carcinoma, n = 2; rectal adenocarcinoma, n = 1) had prolonged disease stabilization that lasted for 16.4, 12.6, and 9.0 months, respectively.

Conclusions:
KA2507 is a potent and selective inhibitor of HDAC6 showing antitumor efficacy and immune modulatory effects in preclinical models. In a phase I study, KA2507 showed selective target engagement, no significant toxicities, and prolonged disease stabilization in a subset of patients. Further clinical studies of KA2507 are warranted, as a single agent or, preferably, combined with other immuno-oncology drugs.
ALK Inhibitors in Neuroblastoma: A Sprint from Bench to Bedside
Authors: Schulte Johannes H. , Eggert Angelika 
Published: May 2021

Abstract
Activating mutations of the anaplastic lymphoma kinase (ALK) gene were identified in the pediatric tumor neuroblastoma, in 2008. Rapid translation of this finding into targeted neuroblastoma therapy was facilitated by the availability of ALK inhibitors developed for adult malignancies and an efficient preclinical and clinical research program.
See related article by Foster et al., p. 3543
Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome
Authors: Mehta Suresh L. , Chokkalla Anil K. , Kim TaeHee , Bathula Saivenkateshkomal , Chelluboina Bharath , Morris-Blanco Kahlilia C. , Holmes Aleah , Banerjee Anik , Chauhan Anjali , Lee Juneyoung , Venna Venugopal R. , McCullough Louise D. , Vemuganti Raghu 
Published: May 2021

Background and Purpose:
Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia. Using FosDT knockout rats, we presently evaluated the role of FosDT in poststroke brain damage.

Methods:

FosDT knockout rats were generated using CRISPR-Cas9 genome editing on a Sprague-Dawley background. Male and female FosDT
−/−
and FosDT
+/+
cohorts were subjected to transient middle cerebral artery occlusion. Postischemic sensorimotor deficits were evaluated between days 1 and 7 and lesion volume on day 7 of reperfusion. The developmental expression profile of FosDT was determined with real-time polymerase chain reaction and mechanistic implications of FosDT in the ischemic brain were conducted with RNA-sequencing analysis and immunostaining of pathological markers.

Results:

FosDT expression is developmentally regulated, with the adult cerebral cortex showing significantly higher FosDT expression than neonates. FosDT
−/−
rats did not show any anomalies in growth and development, fertility, brain cytoarchitecture, and cerebral vasculature. However, when subjected to transient focal ischemia, FosDT
−/−
rats of both sexes showed enhanced sensorimotor recovery and reduced brain damage. RNA-sequencing analysis showed that improved poststroke functional outcome in FosDT
−/−
rats is partially associated with curtailed induction of inflammatory genes, reduced apoptosis, mitochondrial dysfunction, and oxidative stress.

Conclusions:
Our study shows that FosDT is developmentally dispensable, mechanistically important, and a functionally promising target to reduce ischemic brain damage and facilitate neurological recovery.
Dār al-Ṭalīʿah and the Question of Arab Authenticity in the 1960s
Authors: Agbaria Ahmad 
Published: May 2021

Abstract
Cultural institutions and publishing houses have been essential to the making of Arab intellectual conversations in the post-colonial era. The publishing house of Dār al-Ṭalīʿah (est. 1959) played a central role in naturalizing social classifications, ideological views and cultural expectations that have influenced the then-new articulation of the notion of Arab authenticity. Yet, al-Ṭalīʿah was more than a publishing house: it was an intellectual hub that sustained intellectuals and unified them into a coherent group. Despite its centrality, however, the group of authors published by al-Ṭalīʿah has rarely drawn the attention of literary critics or intellectual historians. This article rethinks the connection between ideas and their institutional location, rejecting the conventional view that institutions are only secondary to, or even parasitic on, the supremacy of ideas. Looking at the idea of cultural authenticity (aṣālah) fiercely opposed by al-Ṭalīʿah authors, this article examines the ways the publishing house informed the meaning and deployment of aṣālah during the 1960s, even while rejecting it.
Consumer Protection in Jordanian Discount Sales: A Comparative Study with the Legislations of France, Tunisia and the United Arab Emirates
Authors: Kameel Tariq , Alnusair Fayez , Alhajaya Nour 
Published: May 2021

Abstract
This article compares consumer protection in the framework of discounts with the constituent elements of such sales and the relevant methods of protecting consumer rights, according to French, Emirati, Jordanian, and Tunisian legislation and judicial practice. The findings shed light on the operation of consumer rights and market protection, and argues that each legal system has developed divergent means to attain the same goal. While some legal systems have organised sales with detailed rules, others have engaged in very limited market intervention; in the latter case, consumers are prevented from enjoying an important set of rights, as consumer rights and market protection are determined by the merchants.