bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD
Authors: Kleerekooper Iris , Herbert Megan K , Kuiperij H Bea , Sato Douglas Kazutoshi , Fujihara Kazuo , Callegaro Dagoberto , Marignier Romain , Saiz Albert , Senel Makbule , Tumani Hayrettin , De Jong Brigit A , Trip S Anand , Nakashima Ichiro , Verbeek Marcel M , Petzold Axel 
Published: March 2020

ObjectiveTo explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis.MethodsCerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37).ResultsGFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (rs=0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased.ConclusionsOur data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.
Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management
Authors: O'Brien John , Taylor John Paul , Ballard Clive , Barker Roger A , Bradley Clare , Burns Alistair , Collerton Daniel , Dave Sonali , Dudley Rob , Francis Paul , Gibbons Andrea , Harris Kate , Lawrence Vanessa , Leroi Iracema , McKeith Ian , Michaelides Michel , Naik Chaitali , O'Callaghan Claire , Olsen Kirsty , Onofrj Marco , Pinto Rebecca , Russell Gregor , Swann Peter , Thomas Alan , Urwyler Prabitha , Weil Rimona Sharon , ffytche Dominic 
Published: March 2020

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson’s disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson’s disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.
How to set up a clinical trial
Authors: Thomas Rachel A B , Aitken Emma Louise , Antonelli Jean , Marson Lorna 
Published: March 2020

AbstractClinical trials are considered the gold-standard method for the evaluation of healthcare interventions. However, randomised control trials are complex to perform and many researchers, especially those in the early stages of their career, can find it challenging to know where to start set up, contribute to or lead a trial. This guide provides an introduction to trials and also practical advice to help potential investigators complete their clinical trial to time and to budget by signposting the pathway through the complex regulatory landscape. The authors draw on their own recent experiences of running clinical trials and provide tips and tricks for troubleshooting common problems encountered including trial design and documentation.
Probing new physics signals with symmetry-restored Yukawa textures
Authors: Li Shao-Ping , Li Xin-Qiang 
Published: March 2020

AbstractWe implement a symmetry violation guideline into a two-Higgs-doublet model embedded with three right-handed neutrinos, and exploit the generic Yukawa structures of the model via a hypothetical symmetry restoration of a global $$U_Q(1)^3\times U_L(1)^3$$UQ(1)3×UL(1)3 symmetry. We then apply a mass-powered parametrization to construct the phenomenologically motivated Yukawa interactions, which enables us to incorporate correlatively the neutrino mass, dark matter, as well as the lepton-flavor universality violations in $$R_{K^{(*)}}$$RK(∗) and $$R_{D^{(*)}}$$RD(∗). Specifically, two atmospheric-scale neutrino masses are generated by a low-scale seesaw mechanism, while the much lighter one, being of $$\mathcal {O}(10^{-6})~{{\mathrm{eV}}}$$O(10-6)eV, is fixed by a $$7.1~{\mathrm{keV}}$$7.1keV sterile neutrino dark matter produced primordially by the freeze-in mechanism. On the other hand, the neutrino and the charged-lepton mass hierarchies encoded in the mass-powered textures can naturally account for the $$R_{K^{(*)}}$$RK(∗) and the $$R_{D^{(*)}}$$RD(∗) anomalies, respectively. As a further application, a milder discrepancy of the muon $$g{-}2$$g-2 is observed, which has also been implied by the recently refined lattice results.
Anisotropic Karmarkar stars in f(R, T)-gravity
Authors: Rahaman Monsur , Singh Ksh. Newton , Errehymy Abdelghani , Rahaman Farook , Daoud Mohammed 
Published: March 2020

AbstractThe main aim of this work is devoted to studying the existence of compact spherical systems representing anisotropic matter distributions within the scenario of alternative theories of gravitation, specificallyf(R, T) gravity theory. Besides, a noteworthy and achievable choice on the formulation off(R, T) gravity is made. To provide the complete set of field equations for the anisotropic matter distribution, it is considered that the functional form off(R, T) as$$f(R, T)=R+2\chi T$$f(R,T)=R+2χT, whereRandTcorrespond to scalar curvature and trace of the stress–energy tensor, respectively. Following the embedding class one approach employing the Eisland condition to get a full space–time portrayal interior the astrophysical structure. When the space–time geometry is identified, we construct a suitable anisotropic model by using a new gravitational potential$$g_{rr}$$grrwhich often yields physically motivated solutions that describe the anisotropic matter distribution interior the astrophysical system. The physical availability of the obtained model, represents the physical characteristics of the solution is affirmed by performing several physical tests. It merits referencing that with the help of the observed mass values for six compact stars, we have predicted the exact radii for different values of$$\chi $$χ-coupling parameter. From this one can convince that the solution predicted the radii in good agreement with the observed values. Since the radius of MSP J0740+6620, the most massive neutron star observed yet is still unknown, we have predicted its radii for different values of$$\chi $$χ-coupling parameter. These predicted radii exhibit a monotonic diminishing nature as the parameter$$\chi $$χgoing from$$-1$$-1to 1 gradually. TheM–Rcurve generated from our solution can accommodate a variety of compact stars from the less massive (Her X-1) to super massive (MSP J0740+6620). So the present study uncovers that the modifiedf(R, T) gravity is an appropriate theory to clarify massive astrophysical systems, in any case, for$$\chi =0.0$$χ=0.0the standard consequences of the general relativity are recovered.
Effects of Additives on Structural and Magnetic Properties of Iron Oxide
Authors: Deshmane Vikas V. , Patil Arun V. 
Published: March 2020

This paper analyzes the effects of additives on the properties of Iron oxide. The Iron oxide was synthesized using the co-precipitation method. The X-ray diffraction (XRD) peaks of resultant Iron oxide perfectly matched with JCPDS #860550 ([Formula: see text] phase of Iron oxide / Hematite). The additives like Cobalt oxide, Nickel metal, Indium oxide and Tin metal with diverse properties procured in readymade forms were mechanically mixed with Iron oxide in 1:99, 3:97, 5:95 and 7:93 weight ratios, respectively. The XRD peaks for additives were prominent for 7:93 (Additive: Base Material) weight % ratio samples. Therefore, for further studies, only these samples were used. In this study, variations in XRD intensity, lattice parameters, unit cell volume, grain size, micro-strains (W-H analysis), dislocation density and stacking fault probability were analyzed. The specific surface area of particles was calculated by scanning electron microscope analysis. The presence of additives was also confirmed by energy dispersive spectra (EDS). The M-H loops (Vibrating Sample Magnetometer analysis) for samples under investigation showed rare vertical shifts. The weak magnetic behavior of bare Hematite (1.0 emu/gm) sample improved to antiferromagnetic behavior due to the addition of Cobalt oxide (7.89 emu/gm) and Nickel metal (2.76 emu/gm). The addition of Indium oxide (0.65 emu/gm) and Tin metal (0.73 emu/gm) samples showed a decreased magnetic saturation.
Modelling the evolution of seal integrity in deepwater toe thrust anticlines
Authors: Grant Neil T. 
Published: March 2020

Abstract
This paper describes the results of an empirical one-dimensional model for toe thrust structures that enables both fluid pressure expectations and seal integrity to be evaluated. The growth of a deepwater thrust anticline is forward modelled with calibration made to a present-day structure. Two locations are used to describe the structural evolution: the crest of the anticline and the floor of the adjacent syncline. These locations are followed through structural growth and burial. Pore pressures in the evolving toe thrust are modelled by employing a centroid model for a pre-tectonic target reservoir interval, with shale pressures modelled using the concept of a variable fluid retention depth. A shale compaction model based on critical state soil mechanics is used to model top seal porosity and to aid the evaluation of the capillary top seal. Together with mechanical seal analysis this enables the controls on trapped hydrocarbon column heights to be assessed. Application of the model to two recently drilled toe thrusts is discussed, and results compared to model predictions. The model can be used to offer a generic seal integrity scheme for a toe thrust that may help focus attention on the key exploration risks.
Gradual cold acclimation induces cardioprotection without affecting β-adrenergic receptor-mediated adenylyl cyclase signaling
Authors: Tibenska V. , Benesova A. , Vebr P. , Liptakova A. , Hejnová L. , Elsnicová B. , Drahota Z. , Hornikova D. , Galatík F. , Kolar D. , Vybiral S. , Alánová P. , Novotný J. , Kolar F. , Novakova O. , Zurmanova J. M. 
Published: March 2020

Novel strategies are needed that can stimulate endogenous signaling pathways to protect the heart from myocardial infarction. The present study tested the hypothesis that appropriate regimen of cold acclimation (CA) may provide a promising approach for improving myocardial resistance to ischemia/reperfusion (I/R) injury without negative side effects. We evaluated myocardial I/R injury, mitochondrial swelling, and β-adrenergic receptor (β-AR)-adenylyl cyclase-mediated signaling. Male Wistar rats were exposed to CA (8°C, 8 h/day for a week, followed by 4 wk at 8°C for 24 h/day), while the recovery group (CAR) was kept at 24°C for an additional 2 wk. The myocardial infarction induced by coronary occlusion for 20 min followed by 3-h reperfusion was reduced from 56% in controls to 30% and 23% after CA and CAR, respectively. In line, the rate of mitochondrial swelling at 200 μM Ca2+was decreased in both groups. Acute administration of metoprolol decreased infarction in control group and did not affect the CA-elicited cardiprotection. Accordingly, neither β1-AR-Gsα-adenylyl cyclase signaling, stimulated with specific ligands, nor p-PKA/PKA ratios were affected after CA or CAR. Importantly, Western blot and immunofluorescence analyses revealed β2- and β3-AR protein enrichment in membranes in both experimental groups. We conclude that gradual cold acclimation results in a persisting increase of myocardial resistance to I/R injury without hypertension and hypertrophy. The cardioprotective phenotype is associated with unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca2+-overload. The potential role of upregulated β2/β3-AR pathways remains to be elucidated.NEW & NOTEWORTHY We present a new model of mild gradual cold acclimation increasing tolerance to myocardial ischemia/reperfusion injury without hypertension and hypertrophy. Cardioprotective phenotype is accompanied by unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca2+-overload. The potential role of upregulated β2/β3-adrenoreceptor activation is considered. These findings may stimulate the development of novel preventive and therapeutic strategies against myocardial ischemia/reperfusion injury.
Hybrid Epithelial–Mesenchymal Phenotypes Are Controlled by Microenvironmental Factors
Authors: Selvaggio Gianluca , Canato Sara , Pawar Archana , Monteiro Pedro T. , Guerreiro Patrícia S. , Brás M. Manuela , Janody Florence , Chaouiya Claudine 
Published: March 2020

Abstract

Epithelial-to-mesenchymal transition (EMT) has been associated with cancer cell heterogeneity, plasticity, and metastasis. However, the extrinsic signals supervising these phenotypic transitions remain elusive. To assess how selected microenvironmental signals control cancer-associated phenotypes along the EMT continuum, we defined a logical model of the EMT cellular network that yields qualitative degrees of cell adhesions by adherens junctions and focal adhesions, two features affected during EMT. The model attractors recovered epithelial, mesenchymal, and hybrid phenotypes. Simulations showed that hybrid phenotypes may arise through independent molecular paths involving stringent extrinsic signals. Of particular interest, model predictions and their experimental validations indicated that: (i) stiffening of the extracellular matrix was a prerequisite for cells overactivating FAK_SRC to upregulate SNAIL and acquire a mesenchymal phenotype and (ii) FAK_SRC inhibition of cell–cell contacts through the receptor-type tyrosine-protein phosphatases kappa led to acquisition of a full mesenchymal, rather than a hybrid, phenotype. Altogether, these computational and experimental approaches allow assessment of critical microenvironmental signals controlling hybrid EMT phenotypes and indicate that EMT involves multiple molecular programs.

Significance:
A multidisciplinary study sheds light on microenvironmental signals controlling cancer cell plasticity along EMT and suggests that hybrid and mesenchymal phenotypes arise through independent molecular paths.
Abstract P4-13-10: An evaluation of patient reported outcomes following oncoplastic breast conserving surgery with a crescent modification of the chest wall perforated flap utilizing Breast Q
Authors: Carmichael Amtul R , Sami Amtul Shafee , Mokbel Kefah 
Published: March 2020

Abstract
Background: An increasing acceptance of chest wall perforator flaps has provided additional options for enhancing the cosmetic appearance of the conserved breast after breast cancer surgery. Traditional lateral intercostal anterior perforator (LICAP) flap involves a lateral chest wall scar. To enhance the cosmetic results of LICAP flap, we propose the crescent modification of the LICAP flap to conceal the scar in the inframammary crease.
Aim: The aim of our study was to investigate patient satisfaction and cosmetic outcome by using the BREAST-Q after undergoing crescent-modification of LICAP flap partial breast reconstruction.
Methods: All eighteen consecutive patients with who underwent crescent modification of LICAP flap reconstruction for partial breast reconstruction after wide local excision of breast cancer between June 2017 and July 2019 were invited to complete the BREAST-Q questionnaire. All patients were prospectively evaluated and their demographic, clinical and pathological details were recorded on a database.
Results: The median psychological, physical and sexual well-being scores were 93 (IQR 63-100), 82 (IQR 69-95) and 70 (IQR 46-96) respectively. The median satisfaction score with breast was 88 (IQR 66-100)
Conclusions: In a carefully selected group of women with breast cancer, our study demonstrates that the crescent-modification of the LICAP flap for partial breast reconstruction provides a safe and effective technique with preservation of satisfaction with breast, physical, psychological and sexual well-being.
Citation Format: Amtul R Carmichael, Amtul Shafee Sami, Kefah Mokbel. An evaluation of patient reported outcomes following oncoplastic breast conserving surgery with a crescent modification of the chest wall perforated flap utilizing Breast Q [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-10.
Abstract A58: TGF-beta inhibition and checkpoint blockade in mouse models for gastrointestinal cancer
Authors: Cho Kye S. , Kim Hark K. 
Published: March 2020

Abstract
Background: Gastrointestinal tumors are generally not responsive to checkpoint blockade unless they are hypermutated. Smad4 and p53 are frequently mutated in human gastrointestinal cancer.
Methods: We conducted the intestinal epithelium-specific knockout of Smad4 and Trp53. Transcriptomic profiles were evaluated for spontaneous tumors that formed in these genetically engineered mice.
Results: TGF-beta signaling pathway genes were overexpressed in bulk tumors formed in Villin-Cre;Smad4(F/F);Trp53(F/F). Efficacy of anti-PD-1 (10mg/kg IP BIW) and small-molecule ALK5 inhibitor (25mg/kg PO) was tested in syngeneic mice harboring heterotopic allografts of a cell line that was primarily cultured from a Smad4-null tumor. ALK5 inhibitor did not affect the growth of Smad4-null allograft as a monotherapy, but significantly enhanced the antiproliferative effect of anti-PD-1 as a combination treatment.
Conclusion: TGF-beta pathway inhibition may be a promising approach to increase the efficacy of checkpoint blockade in gastrointestinal tumors. (NCC grants 1910021/1810951.)
Citation Format: Kye S. Cho, Hark K. Kim. TGF-beta inhibition and checkpoint blockade in mouse models for gastrointestinal cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A58.
Ube2v1 Positively Regulates Protein Aggregation by Modulating Ubiquitin Proteasome System Performance Partially Through K63 Ubiquitination
Authors: Xu Na , Gulick James , Osinska Hanna , Yu Yang , McLendon Patrick M. , Shay-Winkler Kritton , Robbins Jeffrey , Yutzey Katherine E. 
Published: March 2020

Rationale:
Compromised protein quality control can result in proteotoxic intracellular protein aggregates in the heart, leading to cardiac disease and heart failure. Defining the participants and understanding the underlying mechanisms of cardiac protein aggregation is critical for seeking therapeutic targets. We identified Ube2v1 (ubiquitin-conjugating enzyme E2 variant 1) in a genome-wide screen designed to identify novel effectors of the aggregation process. However, its role in the cardiomyocyte is undefined.

Objective:

To assess whether Ube2v1 regulates the protein aggregation caused by cardiomyocyte expression of a mutant αB crystallin (CryAB
R120G
) and identify how Ube2v1 exerts its effect.

Methods and Results:

Neonatal rat ventricular cardiomyocytes were infected with adenoviruses expressing either wild-type CryAB (CryAB
WT
) or CryAB
R120G
. Subsequently, loss- and gain-of-function experiments were performed. Ube2v1 knockdown decreased aggregate accumulation caused by CryAB
R120G
expression. Overexpressing Ube2v1 promoted aggregate formation in CryAB
WT
and CryAB
R120G
-expressing neonatal rat ventricular cardiomyocytes. Ubiquitin proteasome system performance was analyzed using a ubiquitin proteasome system reporter protein. Ube2v1 knockdown improved ubiquitin proteasome system performance and promoted the degradation of insoluble ubiquitinated proteins in CryAB
R120G
cardiomyocytes but did not alter autophagic flux. Lys (K) 63-linked ubiquitination modulated by Ube2v1 expression enhanced protein aggregation and contributed to Ube2v1’s function in regulating protein aggregate formation. Knocking out Ube2v1 exclusively in cardiomyocytes by using AAV9 (adeno-associated virus 9) to deliver multiplexed single guide RNAs against Ube2v1 in cardiac-specific Cas9 mice alleviated CryAB
R120G
-induced protein aggregation, improved cardiac function, and prolonged lifespan in vivo.

Conclusions:

Ube2v1 plays an important role in protein aggregate formation, partially by enhancing K63 ubiquitination during a proteotoxic stimulus. Inhibition of Ube2v1 decreases CryAB
R120G
-induced aggregate formation through enhanced ubiquitin proteasome system performance rather than autophagy and may provide a novel therapeutic target to treat cardiac proteinopathies.