bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of Genomic Alterations inIDHWild-Type Glioblastoma Identifies PI3K as a Favorable Prognostic Factor
Authors: Yan Yuanqing , Takayasu Takeshi , Hines Gabriella , Dono Antonio , Hsu Sigmund H. , Zhu Jay-Jiguang , Riascos-Castaneda Roy F. , Kamali Arash , Bhattacharjee Meenakshi B. , Blanco Angel I. , Tandon Nitin , Kim Dong H. , Ballester Leomar Y. , Esquenazi and Yoshua 
Published: June 2020

PURPOSEIDH wild-type (WT) glioblastoma (GBM) is an aggressive tumor with poor survival despite current therapies. The aim of this study was to characterize its genomic profile and determine whether a particular molecular signature is associated with improved survival outcomes.PATIENTS AND METHODSTumor samples from 232 patients with IDH-WT GBM were sequenced, and the landscape of genomic alterations was fully delineated. Genomics data from The Cancer Genome Atlas (TCGA) cohort were analyzed for confirmation. Association of alterations with survival was evaluated in both univariable and multivariable approaches.RESULTSThe genomic landscape of IDH-WT GBM revealed a high frequency of CDKN2A/B loss, TERT promoter mutations, PTEN loss, EGFR alteration, and TP53 mutations. Novel variants or gene mutations, such as ARID1B and MLL2, were identified. To better understand synergistic effects and facilitate decision making for precision medicine, we identified 11 pairs of gene alterations that tended to co-occur or were mutually exclusive, which were confirmed in the TCGA cohort. Survival analysis showed that genomic alterations in TP53 were associated with worse overall survival (OS). However, alterations in PI3K class I genes were associated with significantly better OS (univariable analysis: P = .002; multivariable analysis: hazard ratio [HR], 0.5785; P = .00162) and longer progression-free survival (univariable analysis: P = .0043; multivariable analysis: HR, 0.6228; P = .00913).CONCLUSIONGenomic alterations in PI3K class I are a favorable prognostic factor in IDH-WT GBM. This new prognostic biomarker may facilitate risk stratification of patients, assist in clinical trial enrollment, and provide potential therapeutic targets
Evidence of two types of balance between stem cell mitosis and enterocyte nucleus growth in the Drosophila midgut
Authors: Tamamouna Vasilia , Panagi Myrofora , Theophanous Andria , Demosthenous Maria , Michail Maria , Papadopoulou Markella , Teloni Savvas , Pitsouli Chrysoula , Apidianakis Yiorgos 
Published: June 2020

ABSTRACT
Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult Drosophila midgut of different genetic backgrounds. We provide evidence of two naturally occurring types of balance between mitosis and enterocyte nucleus growth: one based mostly on stem cell mitosis producing new cells and the other based mostly on the degree of young enterocyte nucleus size increase. Mitosis promotes intestinal host defense to infection, but predisposes for dysplasia in the form of stem cell-like clusters. Enterocyte nucleus growth also promotes host defense, without the drawback of promoting dysplasia. Through quantitative genetics, we identified eiger as an autocrine and paracrine inducer of stem cell mitosis. eiger expression in immature epithelial cells tilts the balance towards mitosis and dysplasia via a positive-feedback loop of highly mitotic stem cells sustaining more small nucleus enterocytes, which in turn supply more Eiger.
One-year test-retest reliability of ten vision tests in Canadian athletes
Authors: Aloosh Mehdi , Leclerc Suzanne , Long Stephanie , Zhong Guowei , Brophy James M. , Schuster Tibor , Steele Russell , Shrier Ian 
Published: June 2020

Background: Vision tests are used in concussion management and baseline testing. Concussions, however, often occur months after baseline testing and reliability studies generally examine intervals limited to days or one week. Our objective was to determine the one-year test-retest reliability of these tests. Methods: We assessed one-year test-retest reliability of ten vision tests in elite Canadian athletes followed by the Institut National du Sport du Quebec. We included athletes who completed two baseline (preseason) annual evaluations by one clinician within 365±30 days. We excluded athletes with any concussion or vision training in between the annual evaluations or presented with any factor that is believed to affect the tests (e.g. migraines). Data were collected from clinical charts. We evaluated test-retest reliability using Intraclass Correlation Coefficient (ICC) and 95% limits of agreement (LoA). Results: We examined nine female and seven male athletes with a mean age of 22.7 (SD 4.5) years. Among the vision tests, we observed excellent test-retest reliability in Positive Fusional Vergence at 30cm (ICC=0.93) but this dropped to 0.55 when an outlier was excluded in a sensitivity analysis. There was good to moderate reliability in Negative Fusional Vergence at 30cm (ICC=0.78), Phoria at 30cm (ICC=0.68), Near Point of Convergence break (ICC=0.65) and Saccade (ICC=0.56). The ICC for Positive Fusional Vergence at 3m (ICC=0.56) also decreased to 0.21 after removing one outlier. We found poor reliability in Near Point of Convergence (ICC=0.47), Gross Stereoscopic Acuity (ICC=0.03) and Negative Fusional Vergence at 3m (ICC=0.0). ICC for Phoria at 3m was not appropriate because scores were identical in 14/16 athletes. 95% LoA of the majority of tests were ±40% to ±90%. Conclusions: Five tests had good to moderate one-year test-retest reliability. The remaining tests had poor reliability. The tests would therefore be useful only if concussion has a moderate-large effect on scores.
A non-fluorescent HaloTag blocker for improved measurement and visualization of protein synthesis in living cells
Authors: Cohen Laurie D. , Boulos Ayub , Ziv Noam E. 
Published: June 2020

Background: HaloTag is a modified bacterial enzyme that binds rapidly and irreversibly to an array of synthetic ligands, including chemical dyes. When expressed in live cells in conjunction with a protein of interest, HaloTag can be used to study protein trafficking, synthesis, and degradation. For instance, sequential HaloTag labeling with spectrally separable dyes can be used to separate preexisting protein pools from proteins newly synthesized following experimental manipulations or the passage of time. Unfortunately, incomplete labeling by the first dye, or labeling by residual, trapped dye pools can confound interpretation. Methods: Labeling specificity of newly synthesized proteins could be improved by blocking residual binding sites. To that end, we synthesized a non-fluorescent, cell permeable blocker (1-chloro-6-(2-propoxyethoxy)hexane; CPXH), essentially the HaloTag ligand backbone without the reactive amine used to attach fluorescent groups. Results: High-content imaging was used to quantify the ability of CPXH to block HaloTag ligand binding in live HEK cells expressing a fusion protein of mTurquoise2 and HaloTag. Full saturation was observed at CPXH concentrations of 5-10 µM at 30 min. No overt effects on cell viability were observed at any concentration or treatment duration. The ability of CPXH to improve the reliability of newly synthesized protein detection was then demonstrated in live cortical neurons expressing the mTurquoise2-HaloTag fusion protein, in both single and dual labeling time lapse experiments. Practically no labeling was observed after blocking HaloTag binding sites with CPXH when protein synthesis was suppressed with cycloheximide, confirming the identification of newly synthesized protein copies as such, while providing estimates of protein synthesis suppression in these experiments. Conclusions: CPXH is a reliable (and inexpensive) non-fluorescent ligand for improving assessment of protein-of-interest metabolism in live cells using HaloTag technology.
Promotion Optimization for Multiple Items in Supermarkets
Authors: Cohen Maxime C. , Kalas Jeremy J. , Perakis Georgia 
Published: June 2020

Promotions are a critical decision for supermarket managers, who must decide the price promotions for a large number of items. Retailers often use promotions to boost the sales of the different items by leveraging the cross-item effects. We formulate the promotion optimization problem for multiple items as a nonlinear integer program. Our formulation includes several business rules as constraints. Our demand models can be estimated from data and capture the postpromotion dip effect and cross-item effects (substitution and complementarity). Because demand functions are typically nonlinear, the exact formulation is intractable. To address this issue, we propose a general class of integer programming approximations. For demand models with additive cross-item effects, we prove that it is sufficient to account for unilateral and pairwise contributions and derive parametric bounds on the performance of the approximation. We also show that the unconstrained problem can be solved efficiently via a linear program when items are substitutable and the price set has two values. For more general cases, we develop efficient rounding schemes to obtain an integer solution. We conclude by testing our method on realistic instances and convey the potential practical impact for retailers. This paper was accepted by Yinyu Ye, optimization.
Does Cozen's phenomenon warrant surgical intervention?
Authors: Papamerkouriou Yvonne-Mary , Tsoumpos Pantelis , Tagaris George , Christodoulou George 
Published: June 2020

Purpose Proximal tibial metaphyseal fractures can be complicated by a late valgus deformity, referred to as Cozen's phenomenon. We studied children with such fractures to determine whether the child's age at the time of injury influenced the development of Cozen's as well as the occurrence of elongation. In addition, we explored whether the deformity resolved at long-term follow-up. Methods We conducted a retrospective study of 33 patients (six months to 14 years old). Mean follow-up was 8.8 years (3 to 25). We measured angulation of the fractured limb post-treatment, at maximum deformity and final follow-up, as well as elongation and compared them with the uninjured limb. Results Three of the fractures were treated surgically whereas the rest, nonoperatively. In all, 15 out of 33 fractures developed late valgus deformity between eight and 19 months (mean time 12.5 months). A total of 24 fractures developed elongation. We found no association of either of these with age. Angulation increased to a statistically significant level, from post-treatment to maximum deformity, and then decreased at final follow-up, leaving no statistically significant difference from the initial measurement. The difference in valgus between fractured and uninjured limb increased to a statistically significant level from post-treatment to maximum deformity and then decreased, leaving an excess from the initial measurement. Conclusion In almost half the patients, late valgus deformity developed within two years post-fracture and corrected to the initial post-treatment angles. Patients should be warned of this possibility and reassured of its natural resolution. Level of evidence IV
Clubfoot deformity in the Solomon Islands: Melanesian versus Polynesian ethnicity, a retrospective cohort study
Authors: Todd Maya Rani Louise Chandra , Kodovaru Stephen Sikaveke , Antoniou Georgia , Cundy Peter J. 
Published: June 2020

Purpose Congenital talipes equinovarus (CTEV) has a high incidence in the South Pacific, with New Zealand Maori and Polynesian rates of up to seven per 1000 live births, at least five times higher than the Caucasian population. A genetic component is suggested to explain this, however, there is little information regarding the difference of incidence between Polynesian and Melanesian ethnicity in the South Pacific. Our aim was to investigate the effects of ethnicity on the incidence of CTEV in the Solomon Islands, specifically comparing Melanesian and Polynesian ethnicity. Methods Between 2011 and 2017, data was collected in the Solomon Islands from over 40 clinics upon introduction of the Ponseti programme for treatment of CTEV. Records were kept using the validated Global Clubfoot Initiative data form. Ethnicity was documented, including family history. Results In total, 138 children presented during this period, with 215 affected feet reviewed and treated. In all, 74% of children had solely Melanesian parents and 6% Polynesian. Using the general population ethnic breakdown of 95.3% Melanesian and 3.1% Polynesian, the odds of CTEV in children of Melanesian parents were 0.41 times lower compared with the odds in children of Polynesian parents. Conclusion The results indicate that in the Solomon Islands, CTEV in Melanesian children was less than half as likely to occur in Polynesian children. Our findings also support the theories of minimal Polynesian genetic material persisting in the Solomon Islands and a different genetic risk of CTEV between Polynesians and Melanesians. Level of Evidence III
Highly sensitive multi-stage terahertz parametric detector
Authors: Sakai Hikaru , Kawase Kodo , Murate Kosuke 
Published: June 2020

In this Letter, we developed a high-sensitivity multi-stage terahertz (THz)-wave parametric detection system that operates at room temperature. This detection system has high sensitivity over a wide wavelength range through upconversion of a THz wave to near-infrared light. The broadband noise associated with parametric generation limited the detection sensitivity in the previous setup; however, in the multi-stage configuration using multiple

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crystals, the THz parametric detection sensitivity was improved by spatially eliminating the broadband noise using an iris between the former and latter stages. With this improvement, the minimum detectable sensitivity at 1.05 THz approached 130 zJ (

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J

=

10

−
21

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), which is equivalent to 90 photons or less. Furthermore, by combining this detector with an injection-seeded THz-wave parametric generator, which is a high-power, tunable THz-wave source, the THz-wave measurement system achieved a maximum dynamic range of 125 dB.
Droplet Digital PCR Detects Low-Density Infection in a Significant Proportion of Helicobacter Pylori-Negative Gastric Biopsies of Dyspeptic Patients
Authors: Ramírez-Lázaro María José , Lario Sergio , Quílez María Elisa , Montserrat Antònia , Bella Maria Rosa , Junquera Félix , García-Martínez Lorena , Casalots Àlex , Parra Tamara , Calvet Xavier 
Published: June 2020

INTRODUCTION:

Helicobacter pylori-infected individuals may present low-density infection, undetectable by conventional tests such as histology, rapid urease test, or urea breath test. Droplet digital polymerase chain reaction (ddPCR) is more sensitive than other polymerase chain reaction methods. We aimed to evaluate the ability of ddPCR to detect H. pylori infection in patients diagnosed as negative by conventional tests.

METHODS:
Dyspeptic patients (n = 236) were tested for H. pylori by histology, urea breath test, and rapid urease test. Patients were classified as having 3 positive (n = 25, control group), 2 positive (n = 12), one positive (n = 41), or zero positive (n = 158) diagnostic tests. DNA was extracted from gastric biopsies. Triplicate ddPCR testing for each of the 16S rDNA, ureA, and vacA(s) genes was performed using a QX200 ddPCR system (Bio-Rad). A gene was considered positive when detected by at least 2 of 3 repeated ddPCRs. H. pylori positivity was defined as having 2 or more positive genes.

RESULTS:
All the biopsies of the control patients were positive for all 3 16S rDNA, ureA, and vacA(s) genes. H. pylori infection was detected in 57 (36%), 22 (54%), and 9 (75%) patients with zero, 1, and 2 positive diagnostic tests, respectively. The density of infection was 5, 121, 599, and 3,133 copies of H. pylori genome equivalents for patients with zero, 1, and 2 of 3 positive test results and for the control group, respectively.

DISCUSSION:
ddPCR detected low-density “occult” H. pylori infection in a significant proportion (36%) of patients diagnosed as negative by conventional methods. The number of conventional positive tests was related to the density of infection.
Marxian Socio-Political Economic Theory: Two Schools of Thought: Part-II
Authors: Sehgal M. L. 
Published: June 2020

Marx, an idealist, who believed ‘Capitalism to be an Evil’ and ‘Socialism a Harbinger of Prosperity’, propagated his economic ideas whose basic Pillar was the Labor Theory of Value (LTV) which included Surplus –Value (SV), Falling Tendency of Rate of Profit, Price of a Commodity, Supply and Demand’ Relation, Inflation and Interest Rates. His Socio-political thought included the state would be the Monopolist without anybody owning any private property with religion being the opiate of the masses. He preached class struggle but ignored the middle class. He wanted to do away the State even with the violent Revolution. All this brought him in conflict both with his contemporary economists as well as with the future generation of economists. The 150 old Socio-political Economic Theory of Marx, though a noble idea, could not stand the test of the times and started falling under its weight. The duality in the minds of the people about its utility and applicability is best described by the celebrated Physicist- Einstein’s viewpoint which speaks volumes of the aura of the man named Karl Heinrich Marx:
“I am convinced (that) there is only one way to eliminate these grave evils, namely through the establishment of a socialist economy, accompanied by an educational system which would be oriented toward social goals. In such an economy, the means of production are owned by society itself and are utilized in a planned fashion. A ‘planned economy’, which adjusts production to the needs of the community, would distribute the work to be done among all those able to work and would guarantee a livelihood to every man, woman, and child”
But look at the lurking fear in the mind of the genius about the ‘planned economy’ as:
“Nevertheless, it is necessary to remember that a planned economy is not yet socialism. A planned economy as such may be accompanied by the ‘complete enslavement of the individual’. The achievement of socialism requires the solution of some extremely difficult socio-political problems: how is it possible, because of the far-reaching ‘centralization of political and economic power’, to ‘prevent bureaucracy from becoming all-powerful and overweening’? How can the ‘rights of the individual be protected’ and therewith a ‘democratic counterweight to the power of bureaucracy be assured’?”
Development of assisted reproductive technology services in Thailand between 2008 and 2014 before the new law: Results generated from the National ART Registry, Royal Thai College of Obstetricians and Gynecologists
Authors: Chiamchanya Charoenchai , Pruksananonda Kamthorn 
Published: June 2020

Abstract

Background
While the assisted reproductive technology (ART) relieves the burden of infertility in many couples, it presents significant public health challenges due to the substantial risk for multiple birth delivery and preterm birth, which are associated with poor maternal and fetal health outcomes. For this reason, it is important to monitor the development and effectiveness of ART services in Thailand.

Objective
To analyze the trends of ART services in Thailand between 2008 and 2014.

Methods
ART clinics in Thailand are required to submit data to the Royal Thai College of Obstetricians and Gynecologists via the National Reporting System. The data from 2008 to 2014 were collected and analyzed.

Results
The number of ART centers was increased from 35 to 47. The total fresh ART cycles were also increased from 3,723 to 6,516. The percentage values of intracytoplasmic sperm injection (ICSI), in vitro fertilization, gamete intrafallopian transfer, and zygote intrafallopian transfer cycles were changed from 77.87 to 95.59, 21.43 to 4.31, 0.21 to 0.09, and 0.45 to 0.05, respectively. The clinical pregnancy rates were 28.79–33.19, 22.84–51.34, 14.29–42.86, and 0.00–26.67, respectively. The clinical pregnancy rates in fresh vs. frozen-thawed cycles were 31.01–36.33 vs. 31.54–37.34 (P < 0.05). The clinical pregnancy rates in female age <35 vs. 35–39 vs. ≥40 years were 36.97–40.70 vs. 32.74–33.42 vs. 21.08–31.34, respectively (P < 0.001), and the percentage values of multifetal pregnancy rate were 18.75 vs. 13.30 and 13.69, respectively (P < 0.001). There were increasing preimplantation genetic screening (PGS) cycles, with the percentage of the clinical pregnancy rate (25.90–42.63, P < 0.05). The clinical pregnancy rates in medium-sized ART centers (100–300 cycles per year) vs. in small and large centers were 30.79–41.14 vs. 28.01–34.04 and 8.70–40.35, respectively (P < 0.001). Trends of increasing percentage of ART birth rate to total birth rate ratio were 0.24–0.34 (P < 0.05).

Conclusions
There were higher clinical pregnancy rates in frozen-thawed cycles. Higher multifetal pregnancy rate and clinical pregnancy rate were also found in younger females. There were increasing uses of ICSI and PGS. A trend toward increasing ART birth to total birth ratio was observed.
Das Werk als Nutzungsobjekt in den Schranken für Lehre, Forschung und Bibliotheken (§§ 60a, 60c, 60e UrhG)
Authors: Gräbitz Anja 
Published: June 2020

Abstract
Dieser Artikel behandelt die neu geschaffenen Schranken für Lehre, Forschung und Bibliotheken (§§ 60a, 60c, 60e UrhG), welche die Nutzung eines urheberrechtlich geschützten Werks in unterschiedlichem Umfang erlauben. Für die einzelnen Schrankenregelungen werden jeweils deren Tatbestände, Erweiterungen und gegebenenfalls die entsprechenden Bereichsausnahmen ausführlich dargestellt. Dabei wird an den entsprechenden Stellen auf die praktischen Probleme bei der Anwendung der Schrankenbestimmungen näher eingegangen.
Properties of Laser Additive Deposited Metallic Powder of Inconel 625
Authors: Danielewski Hubert , Antoszewski Bogdan 
Published: June 2020

Abstract
Paper presents results of laser additive manufacturing. Deposition of nickel based super alloy Inconel 625 was performed. Laser metal deposition is advanced manufacturing process dedicated for prototyping and low scale series production. Inconel 625 is nickel based super alloy, with high heat resistance properties. Therefore due material properties and chemical composition is characterized as a difficult to machining [1, 2]. Additive manufacturing process using focused photons beam for selective deposition of metallic powder in laser engineered net shaping (LENS) method can be used as alternative technology. High energy density of controllable laser beam combining with coaxial delivery system allow to precise deposited metallic powder. Manufacturing process are based on selective melting of additional material using laser radiation and crystallization process. An additional material in form of filler wire as well as metallic powder can be used. Advantages of using metallic powder are higher level of process control, nevertheless adequate selection of process parameters are required. High energy density of laser beam and rapid crystallization process affect on metallographic structure of deposited material. Thermal energy absorbed in material affect on phase transformation.Molten powder mixing with base material changing metallographic structure. Chemical composition of obtained overlay weld are combination of base and additive material. Therefore to achieve stable crystallization process chemical composition of additive material wassimilar to base material. Additional alloying elements could affect on mechanical properties. Deposition process using TruLaserCell 1005 laser machine was performed. To determine properties of manufactured material metallographic analysis and destructive tests were performed.