bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introduction of nucleic acid amplification technology for blood screening in Hungary
Authors: Siposné Sohajda Réka , Kokavecz László , Baróti‐Tóth Klára , Nagy Sándor , Paholcsek Melinda , Stágel Anikó 
Published: February 2021

Background & AimsWith this study, we intended to report our experiences about introducing nucleic acid testing for blood donation screening for human immunodeficiency virus, hepatitis B and C in Hungary. This study summarizes the experiences of nucleic acid amplification technology (NAT) screening of the first 16 months.MethodsThe study was conducted from 5 June 2018 to 30 September 2019 in two phases. During the first 7 months of the study, the NAT tests were performed in parallel with serology. The yields of the methods were compared. After the initial seven months, only seronegative samples were tested by NAT. NAT tests were performed in minipools of 96.ResultsIn this 16‐month period, nearly 400 000 donations were screened by NAT. During the first phase, almost 150 000 samples were tested in parallel by serology and NAT screening. NAT screening during Phase I failed to identify 4 HCV‐ and 1 HBV‐reactive donations. In the second phase, about 245 000 seronegative samples were screened, with only one HBV reactive yield.ConclusionsNucleic acid amplification technology testing proven to be an optimal diagnostic adjunct to serological screening, since it can help to identify early window period infections and occult hepatitis B infections. According to our experience however, the used pooling strategy represents a dilution rate of nucleic acid targets, which makes identifying these types of infections difficult. According to our cost–benefit analysis, reducing the pool size to 60 would result in a 60% sensitivity increase, at the expense of increasing the daily costs by 25%.
Comparison of murine behavioural and physiological responses after forced exercise by electrical shock versus manual prodding
Authors: Khataei Tahsin , Romig‐Martin Sara A. , Harding Anne Marie S. , Radley Jason J. , Benson Christopher J. 
Published: February 2021

New Findings

What is the central question of this study?
Forced treadmill exercise using electrical shock is the most common technique in rodent exercise studies. Here, we examined how the use of electrical shock during forced treadmill exercise affects behavioural and physiological responses in comparison to a novel non‐electrical shock technique.

What is the main finding and its importance?
In comparison to mice that underwent traditional treadmill running induced by electrical shock, mice that underwent forced running using a novel technique involving gentle prodding to induce running showed: (i) higher locomotor activity; (ii) less anxiety‐like behaviour; and (iii) altered exercise‐induced muscle pain immediately after exercise.

AbstractAnimal models of exercise have been useful to understand underlying cellular and molecular mechanisms. Many studies have used methods of exercise that are unduly stressful (e.g., electrical shock to force running), potentially skewing results. Here, we compared physiological and behavioural responses of mice after exercise induced using a prodding technique that avoids electrical shock versus a traditional protocol using electrical shock. We found that exercise performance was similar for both techniques; however, the shock group demonstrated significantly lower locomotor activity and higher anxiety‐like behaviour. We also observed divergent effects on muscle pain; the prodding group showed hyperalgesia immediately after exercise, whereas the shock group showed hypoalgesia. Corticosterone concentrations were elevated to a similar extent for both groups. In conclusion, mice that were exercised without shock generated similar maximal exercise performance, but postexercise these mice showed an increase in locomotor activity, less anxiety‐like behaviour and altered muscle pain in comparison to mice that exercised with shock. Our data suggest that running of mice without the use of electrical shock is potentially less stressful and might be a better technique to study the physiological and behavioural responses to exercise.
Contrast sensitivity function in patients with macular disease and good visual acuity
Authors: Wai Karen M , Vingopoulos Filippos , Garg Itika , Kasetty Megan , Silverman Rebecca F , Katz Raviv , Laíns Inês , Miller Joan W , Husain Deeba , Vavvas Demetrios G , Kim Leo A , Miller John B 
Published: February 2021

IntroductionContrast sensitivity function (CSF) may better estimate a patient’s visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity.MethodsPatients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA ≥20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd.Results151 eyes with maculopathy and 93 control eyes with VA ≥20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: −0.174; p<0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: −0.094 to −0.200 log CS, all p<0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd).ConclusionCSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods.
Psychosocial influences on help-seeking behaviour for cancer in low-income and lower middle-income countries: a mixed-methods systematic review
Authors: McCutchan Grace , Weiss Bahr , Quinn-Scoggins Harriet , Dao Anh , Downs Tom , Deng Yunfeng , Ho Ha , Trung Lam , Emery Jon , Brain Kate 
Published: February 2021

IntroductionStarting cancer treatment early can improve outcomes. Psychosocial factors influencing patients’ medical help-seeking decisions may be particularly important in low and lower middle-income countries (LMIC) where cancer outcomes are poor. Comprehensive review evidence is needed to understand the psychosocial influences on medical help-seeking for cancer symptoms, attendance for diagnosis and starting cancer treatment.MethodsMixed-methods systematic review registered on PROSPERO (CRD42018099057). Peer-reviewed databases were searched until April 2020 for studies assessing patient-related barriers and facilitators to medical help-seeking for cancer symptoms, diagnosis and treatment in adults (18+ years) living in LMICs. Quality of included studies was assessed using the Critical Appraisal Skills Programme tool. Data were synthesised using meta-analytic techniques, meta-ethnography or narrative synthesis as appropriate.ResultsOf 3963 studies identified, 64 were included. In quantitative studies, use of traditional, complementary and alternative medicine (TCAM) was associated with 3.60 higher odds of prolonged medical help-seeking (95% CI 2.06 to 5.14). Qualitative studies suggested that use of TCAM was a key barrier to medical help-seeking in LMICs, and was influenced by causal beliefs, cultural norms and a preference to avoid biomedical treatment. Women face particular barriers, such as needing family permission for help-seeking, and higher stigma for cancer treatment. Additional psychosocial barriers included: shame and stigma associated with cancer such as fear of social rejection (eg, divorce/disownment); limited knowledge of cancer and associated symptoms; and financial and access barriers associated with travel and appointments.ConclusionDue to variable quality of studies, future evaluations would benefit from using validated measures and robust study designs. The use of TCAM and gender influences appear to be important barriers to help-seeking in LMIC. Cancer awareness campaigns developed with LMIC communities need to address cultural influences on medical help-seeking behaviour.
Development of a poly-axial platen for testing true-triaxial behavior of rocks
Authors: Garg Prasoon , Pandit Bhardwaj , Mishra Brijes , Sivakumar Babu G.L. 
Published: February 2021

Mining at greater depths can lead to stress-induced failure, especially in areas of high horizontal in situ stress. The induced stresses around the opening are known to be in a poly-axial stress state where, σ1 ≠ σ2 ≠ σ3 with special case of σ3 = 0 and σ1, σ2 ≠ 0 at its boundary, where σ1, σ2, σ3 are major, intermediate, minor principal stress, respectively. The conventional triaxial testing does not represent the actual in situ strength of the rock in regions of high horizontal stress, as it ignores the influence of intermediate principal stress (σ2). The typical poly-axial testing (biaxial and true-triaxial tests) of intact rock mostly requires sophisticated and expensive loading systems. This study investigated the mechanical behavior of intact rock under a poly-axial stress state using a simple and cost-effective design. The apparatus consists of a biaxial frame and a confining device. The biaxial frame has two platens that apply equal stress in both directions (σ1 = σ2) on a 50.8 mm cubical specimen when placed inside the uniaxial loading device. The confining device performed separate biaxial tests under constant intermediate principal stress (σ2 = constant) and true-triaxial tests when used along with the biaxial frame. This study then compared the failure modes and peak strength of Berea sandstone specimens with other biaxial–triaxial devices to validate the design of the poly-axial apparatus. We also performed uniaxial tests on both standard cylindrical samples and prismatic specimens of different slenderness ratios. These tests provided a complete understanding of the failure mode transition from standard uniaxial compressive tests to triaxial stress conditions on cubical specimens. Additionally, this study determined best-fitted strength envelopes for biaxial and triaxial stress state. Based on regression analysis, we found a quadratic polynomial to be a good fit to biaxial strength envelope. For the true-triaxial strength envelope, we found the three-dimensional (3D) failure criterion to be a good fit with R2 of 0.964.
Euler–Heisenberg waves propagating in a magnetic background
Authors: Guzman-Herrera Elda , Breton Nora 
Published: February 2021

AbstractWe derive the Euler–Heisenberg solutions that describe electromagnetic waves propagating through very intense uniform magnetic or electric background, with the effective metric approach. We first explore the case of a magnetic background: as a result of the interaction between the wave and the background there is birefringence and a longitudinal electric field component arises. The two phase velocities depend on the intensity of the external magnetic field and on the polarization of the wave; phase velocities can be slowed down up to the order of hundred thousandths for fields $$B/B_\mathrm{cr}<< 1$$

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. The analogous study is done when the wave propagates through a uniform electric field. We then consider the situation when the background is in movement by means of a Lorentz boost, modeling then a magnetized flowing medium. We determined how this motion affects the speed of propagation of the electromagnetic wave, in this case the phase velocities depend on both the magnetic background and the direction and velocity of the boost.
Weak gravitational lensing Schwarzschild-MOG black hole in plasma
Authors: Atamurotov Farruh , Abdujabbarov Ahmadjon , Rayimbaev Javlon 
Published: February 2021

AbstractThis paper is devoted to study weak gravitational lensing properties around black hole surrounded plasma medium in modified gravity (MOG). We have investigated the effects of the MOG-parametr and plasma medium on the deflection angle and total magnification of the images. we have presented the comparisons of the effects of the uniform plasma, singular isothermal sphere and non-singular isothermal sphere. We have also shown that the uniform plasma effects significantly stronger than the other models of plasma medium.Through the studies of the total magnifications of images of a remote source we have shown that the effects of the MOG parameter and plasma medium are similar and the increase of the MOG parameter and plasma frequency cause to increase the total magnification. Moreover, we have explored and analyzed how the MOG effects can reflect the plasma medium providing the same values of the total magnification of images.
Effects of extended uncertainty principle on the relativistic Coulomb potential
Authors: Hamil B. , Merad M. , Birkandan T. 
Published: February 2021

The relativistic bound-state energy spectrum and the wave functions for the Coulomb potential are studied for de Sitter and anti-de Sitter spaces in the context of the extended uncertainty principle. Klein–Gordon and Dirac equations are solved analytically to obtain the results. The electron energies of hydrogen-like atoms are studied numerically.
Targeting the platelet-derived growth factor receptor α with a neutralizing human monoclonal antibody inhibits the growth of tumor xenografts: Implications as a potential therapeutic target
Authors: Loizos Nick , Xu Yan , Huber Jim , Liu Meilin , Lu Dan , Finnerty Bridget , Rolser Robin , Malikzay Asra , Persaud Anita , Corcoran Erik , Deevi Dhanvanthri S. , Balderes Paul , Bassi Rajiv , Jimenez Xenia , Joynes Christopher J. , Mangalampalli Venkata R.M. , Steiner Philipp , Tonra James R. , Wu Yan , Pereira Daniel S. , Zhu Zhenping , Ludwig Dale L. , Hicklin Daniel J. , Bohlen Peter , Witte Larry , Kussie Paul 
Published: February 2021

Abstract
Platelet-derived growth factor receptor α (PDGFRα) is a type III receptor tyrosine kinase that is expressed on a variety of tumor types. A neutralizing monoclonal antibody to human PDGFRα, which did not cross-react with the β form of the receptor, was generated. The fully human antibody, termed 3G3, has a Kd of 40 pmol/L and blocks both PDGF-AA and PDGF-BB ligands from binding to PDGFRα. In addition to blocking ligand-induced cell mitogenesis and receptor autophosphorylation, 3G3 inhibited phosphorylation of the downstream signaling molecules Akt and mitogen-activated protein kinase. This inhibition was seen in both transfected and tumor cell lines expressing PDGFRα. The in vivo antitumor activity of 3G3 was tested in human glioblastoma (U118) and leiomyosarcoma (SKLMS-1) xenograft tumor models in athymic nude mice. Antibody 3G3 significantly inhibited the growth of U118 (P = 0.0004) and SKLMS-1 (P &lt; 0.0001) tumors relative to control. These data suggest that 3G3 may be useful for the treatment of tumors that express PDGFRα.
The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15
Authors: Kim Jong-Sik , Baek Seung Joon , Sali Tina , Eling Thomas E. 
Published: February 2021

Abstract
Although the chemopreventive and antitumorigenic activities of nonsteroidal anti-inflammatory drug (NSAID) against colorectal cancer are well established, the molecular mechanisms responsible for these properties in ovarian cancer have not been elucidated. Therefore, there is an urgent need to develop mechanism-based approaches for the management of ovarian cancer. To this end, the effect of several NSAIDs on ovarian cancer cells was investigated as assessed by the induction of NAG-1/MIC-1/GDF-15, a proapoptotic gene belonging to the transforming growth factor-β superfamily. Sulindac sulfide was the most significant NSAID activated gene 1 (NAG-1) inducer and its expression was inversely associated with cell viability as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. This growth suppression by sulindac sulfide was recovered by transfection of NAG-1 small interfering RNA. These results indicate that NAG-1 is one of the genes responsible for growth suppression by sulindac sulfide. Furthermore, we observed down-regulation of p21 WAF1/CIP1 by introduction of NAG-1 small interfering RNA into sulindac sulfide–treated cells. In addition, to elucidate other potential molecular mechanisms involved in sulindac sulfide treatment of ovarian cancer cells, we did a membrane-based microarray experiment. We found that cyclin D1, MMP-1, PI3KR1, and uPA were down-regulated by sulindac sulfide. In conclusion, a novel molecular mechanism is proposed to explain the experimental results and provide a rationale for the chemopreventive activity of NSAIDs in ovarian cancer.
Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron-restrictive silencer factor, which can be functionally countered by REST-VP16
Authors: Fuller Gregory N. , Su Xiaohua , Price Roger E. , Cohen Zvi R. , Lang Frederick F. , Sawaya Raymond , Majumder Sadhan 
Published: February 2021

Abstract
Medulloblastoma, one of the most malignant pediatric brain tumors, is believed to arise from the undifferentiated external granule-layer cells in the cerebellum. It is a heterogeneous cancer, and the mechanism of tumorigenesis for the majority of types is unknown. Repressor element-1 silencing transcription/neuron-restrictive silencer factor (REST/NRSF) is a transcriptional repressor that can block transcription of a battery of neuronal differentiation genes by binding to a specific consensus DNA sequence present in their regulatory region. Previously, we found that some medulloblastoma cell lines express REST/NRSF at high levels compared with either neuronal progenitor cells or fully differentiated neurons. However, it is not known if REST/NRSF is indeed overexpressed in human medulloblastoma tumor specimens and in what frequency. Here, we did an immunohistochemical analysis of such tumor specimens using an anti-REST antibody. We show that among 21 human medulloblastoma tumors, 17 expressed REST/NRSF (6 strongly and 11 weakly). In contrast, adjacent normal cerebellum tissue sections and four of the tumor specimens did not express REST/NRSF, indicating that abnormal expression of REST/NRSF is observed in the majority of human medulloblastoma tumors. To determine whether countering REST/NRSF activity blocks tumorigenicity of medulloblastoma cells, especially in the intracranial (i.c.) environment, we found that adenovirus-mediated expression of REST-VP16, a recombinant transcription factor that can compete with REST/NRSF and activate REST/NRSF target genes instead of repressing them, blocked the i.c. tumorigenic potential of medulloblastoma cells and inhibited growth of established tumors in nude mice, suggesting that REST/NRSF may serve as a therapeutic target for medulloblastoma and that forced expression of neuronal differentiation genes in medulloblastoma cells through agents, such as REST-VP16, can interfere with their tumorigenicity.
Chemosensitivity profile of cancer cell lines and identification of genes determining chemosensitivity by an integrated bioinformatical approach using cDNA arrays
Authors: Nakatsu Noriyuki , Yoshida Yoko , Yamazaki Kanami , Nakamura Tomoki , Dan Shingo , Fukui Yasuhisa , Yamori Takao 
Published: February 2021

Abstract
We have established a panel of 45 human cancer cell lines (JFCR-45) to explore genes that determine the chemosensitivity of these cell lines to anticancer drugs. JFCR-45 comprises cancer cell lines derived from tumors of three different organs: breast, liver, and stomach. The inclusion of cell lines derived from gastric and hepatic cancers is a major point of novelty of this study. We determined the concentration of 53 anticancer drugs that could induce 50% growth inhibition (GI50) in each cell line. Cluster analysis using the GI50s indicated that JFCR-45 could allow classification of the drugs based on their modes of action, which coincides with previous findings in NCI-60 and JFCR-39. We next investigated gene expression in JFCR-45 and developed an integrated database of chemosensitivity and gene expression in this panel of cell lines. We applied a correlation analysis between gene expression profiles and chemosensitivity profiles, which revealed many candidate genes related to the sensitivity of cancer cells to anticancer drugs. To identify genes that directly determine chemosensitivity, we further tested the ability of these candidate genes to alter sensitivity to anticancer drugs after individually overexpressing each gene in human fibrosarcoma HT1080. We observed that transfection of HT1080 cells with the HSPA1A and JUN genes actually enhanced the sensitivity to mitomycin C, suggesting the direct participation of these genes in mitomycin C sensitivity. These results suggest that an integrated bioinformatical approach using chemosensitivity and gene expression profiling is useful for the identification of genes determining chemosensitivity of cancer cells.
Imatinib and gastrointestinal stromal tumors: Where do we go from here?
Authors: De Giorgi Ugo , Verweij Jaap 
Published: February 2021

Abstract
Imatinib has tremendously changed the treatment of gastrointestinal stromal tumor (GIST). Research is currently focusing on its optimal use and the mechanisms of resistance that may emerge. A multidisciplinary approach including medical oncologists, surgeons, radiologists, and pathologists is crucial for the optimal management of these patients. Moreover, imatinib treatment in GIST represents an extraordinary model to expand our knowledge on the molecular mechanisms that are basic to the effects of molecularly targeted therapies. This review summarizes the existing knowledge of the imatinib treatment in GIST and describes directions for further development.
Abstract IA02: A case for priming, not checkpoint
Authors: Vonderheide Robert H. 
Published: February 2021

Abstract
Most tumors are unresponsive to immune checkpoint blockade, especially if deep immunosuppression in the tumor develops prior to and prevents T cell immunosurveillance. Failed or frustrated T cell priming often needs repair before successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical role in generating T cell immunity, by activating dendritic cells, and converting cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate T cell-dependent anti-tumor activity, especially in combination with chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With the advent of multiple CD40 agonists with acceptable single-agent toxicity, clinical evaluation of CD40 combinations has accelerated.
Citation Format: Robert H. Vonderheide. A case for priming, not checkpoint [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA02.