bluuebunny/crossref_metadata_2025_split huggingface dataset:
MLN0264, an investigational, first-in-class antibody-drug conjugate (ADC) targeting guanylyl cyclase C (GCC): Phase I, first-in-human study in patients (pts) with advanced gastrointestinal (GI) malignancies expressing GCC.
Authors: Almhanna Khaldoun , Messersmith Wells A. , Rodon Ahnert Jordi , Cruz Cristina , Ryan David P. , Jung JungAh , Fasanmade Adedigbo , Wyant Tim , Kalebic Thea 
Published: March 2020

TPS3646 Background: MLN0264, an investigational ADC that targets GCC, consists of a fully human monoclonal antibody conjugated to the cytotoxic microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. MMAE and the linker technology are licensed from Seattle Genetics. GCC is a cell surface protein expressed by normal intestinal epithelial cells, ~95% of metastatic colorectal cancer (mCRC), and subsets of gastric and pancreatic cancers. In normal tissue, GCC is expressed on the apical side of epithelial cell tight junctions; therefore, systemically delivered GCC-targeting agents are expected to be preferentially delivered to tumor tissue in which cell polarity is disrupted. MLN0264 has demonstrated antitumor activity in mouse xenograft models of GCC-expressing tumors (Veiby et al. EORTC-NCI-AACR, 2012), supporting the scientific rationale for this first-in-human study. Methods: This study (NCT01577758) was designed to evaluate MLN0264 in ~60 adult pts with GI malignancies expressing GCC (≥1+), measurable disease by RECIST, and ECOG PS 0/1. This study is being conducted at 4 centers in the US and EU and is estimated to last ~36–42 months. Pts receive IV MLN0264 on day 1 of 21-day cycles for up to 17 cycles or until disease progression/unacceptable MLN0264-related toxicity. Dose escalation is proceeding via an adaptive Bayesian continual reassessment model approach based on dose-limiting toxicities in cycle 1. Following determination of the maximum tolerated dose (MTD), up to 14 pts each will be enrolled to mCRC and gastric carcinoma expansion groups to further characterize the safety, tolerability, and pharmacokinetics (PK) of MLN0264 and evaluate its clinical activity. The primary objectives are to evaluate the safety and tolerability, determine the MTD, and describe the PK of IV MLN0264. Secondary objectives are to evaluate the antitumor activity and immunogenicity of MLN0264. An exploratory objective is to examine the relationship between levels of GCC protein expression in tumor tissue and clinical response. Enrollment as of Jan 2013 was 12 pts. Clinical trial information: NCT01577758.
Gender Differences in the Response to Short-term Cold Exposure in Young Adults
Authors: Mengel Laura A , Seidl Hatti , Brandl Beate , Skurk Thomas , Holzapfel Christina , Stecher Lynne , Claussnitzer Melina , Hauner Hans 
Published: March 2020

Abstract

Context
Cold exposure (CE) has been shown to enhance energy expenditure by activating brown adipose tissue thermogenesis and metabolism in humans. However, it remains to be elucidated if there are gender-specific differences in cold-induced thermogenesis and metabolism.

Objective
To study the impact of mild CE on resting energy expenditure (REE) and metabolism in males compared with females.

Setting
A cross-sectional study.

Participants
117 healthy young Caucasians participated in this study (58 males). Mean age was 25.1 ± 3.6 years and mean body mass index 22.3 ± 1.7 kg/m2.

Intervention
Participants underwent a short-term CE using water perfused mattresses to activate nonshivering thermogenesis.

Main Outcome Measures
REE was assessed before and 2 hours after CE followed by blood sampling. Selected metabolites and hormones were measured. Skin temperatures were monitored at various sites throughout the experiment.

Results
Participants showed a significant increase in REE after CE (6.5%, P &lt; .001). This increase did not differ between genders (P = .908). However, there were differences between males and females in changes of plasma glucose (–5.1% versus –7.4%, P = .024), leptin (–14.3% versus –30.1%, P &lt; .001) and adiponectin (5.4% versus 12.8%, P = .018) after CE. We observed a significant decrease of the supraclavicular skin temperature in men (–0.3%, P = .034), but not in women (0.3%, P = .326)(P = .019 between genders).

Conclusions
We did not observe a difference in the thermogenic response, measured as change of REE, to CE in women compared with men. However, we found that some metabolic and hormonal changes were more pronounced in women than in men suggesting a gender-specific response to cold.
Glycemic Measures and Development and Resolution of Nonalcoholic Fatty Liver Disease in Nondiabetic Individuals
Authors: Wang Bin , Li Mian , Zhao Zhiyun , Wang Shuangyuan , Lu Jieli , Chen Yuhong , Xu Min , Wang Weiqing , Ning Guang , Bi Yufang , Wang Tiange , Xu Yu 
Published: March 2020

Abstract

Context
Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD); however, evidence regarding the link between blood glucose, especially below the threshold for T2D, and NAFLD is scarce.

Objective
The objective of this work is to examine the associations of fasting glucose, oral glucose tolerance test (OGTT) 2-hour glucose, and hemoglobin A1c (HbA1c), and changes in these measures with development and resolution of NAFLD in nondiabetic individuals.

Methods
This longitudinal cohort study comprised 4273 Chinese adults age 40 years or older and free of baseline T2D from 2010 to 2015. Blood sampling was performed during the OGTT test. NAFLD was ascertained by hepatic ultrasonography. Risk ratios (RRs) were calculated using modified Poisson regression models.

Results
During a mean 4.4 years of follow-up, NAFLD occurred in 573 (17.9%) of the 3209 participants without baseline NAFLD and resolved in 304 (28.6%) of the 1064 participants with baseline NAFLD. OGTT 2-h glucose was positively associated with NAFLD incidence (RR per 1-SD increase: 1.16, 95% CI: 1.08-1.25), whereas fasting (RR: 0.86, 95% CI: 0.78-0.94) and 2-hour glucose (RR: 0.85, 95% CI: 0.77-0.93) were inversely associated with resolution of NAFLD. Glycemic deterioration conferred increased risk of developing NAFLD and decreased likelihood of resolution of NAFLD than maintaining normal glycemic regulation (NGR). The strongest associations were observed for individuals who developed T2D. Meanwhile, baseline or incident NAFLD significantly increased the risk of deterioration in glucose metabolism.

Conclusions
Increased glycemic levels within the nondiabetic range, as well as progression from NGR to T2D or prediabetes, were adversely associated with development and improvement of NAFLD.
Fractures, Bone Mineral Density, and Final Height in Craniopharyngioma Patients with a Follow-up of 16 Years
Authors: van Santen Selveta S , Olsson Daniel S , van den Heuvel-Eibrink Marry M , Wijnen Mark , Hammarstrand Casper , Janssen Joseph A M J L , Johannsson Gudmundur , van der Lely Aart J , Neggers Sebastian J C M M 
Published: March 2020

Abstract

Context
Pituitary hormonal deficiencies in patients with craniopharyngioma may impair their bone health.

Objective
To investigate bone health in patients with craniopharyngioma.

Design
Retrospective cross-sectional study.

Setting
Dutch and Swedish referral centers.

Patients
Patients with craniopharyngioma (n = 177) with available data on bone health after a median follow-up of 16 years (range, 1-62) were included (106 [60%] Dutch, 93 [53%] male, 84 [48%] childhood-onset disease).

Main outcome measures
Fractures, dual X-ray absorptiometry-derived bone mineral density (BMD), and final height were evaluated. Low BMD was defined as T- or Z-score ≤-1 and very low BMD as ≤-2.5 or ≤-2.0, respectively.

Results
Fractures occurred in 31 patients (18%) and were more frequent in men than in women (26% vs. 8%, P = .002). Mean BMD was normal (Z-score total body 0.1 [range, -4.1 to 3.5]) but T- or Z-score ≤-1 occurred in 47 (50%) patients and T-score ≤-2.5 or Z-score ≤-2.0 in 22 (24%) patients. Men received less often treatment for low BMD than women (7% vs. 18%, P = .02). Female sex (OR 0.3, P = .004) and surgery (odds ratio [OR], 0.2; P = .01) were both independent protective factors for fractures, whereas antiepileptic medication was a risk factor (OR, 3.6; P = .03), whereas T-score ≤-2.5 or Z-score ≤-2.0 was not (OR, 2.1; P = .21). Mean final height was normal and did not differ between men and women, or adulthood and childhood-onset patients.

Conclusions
Men with craniopharyngioma are at higher risk than women for fractures. In patients with craniopharyngioma, a very low BMD (T-score ≤-2.5 or Z-score ≤-2.0) seems not to be a good predictor for fracture risk.
Sweet taste does not modulate pain perception in adult humans
Authors: Mooney Elizabeth R , Davies Alexander J , Pickering Anthony E 
Published: March 2020

Background: It is commonly observed that humans who are in pain or discomfort seek solace in the form of sweet foods and drinks. Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.
Maghreb forever: From Third-Worldism to the epistemology of multiplicity in media culture
Authors: Ritzer Ivo 
Published: March 2020

Abstract
Focusing on Post-Third Cinema in the Maghreb, this article analyses productions that break ith both the elitism and the nativist agenda of Third Cinema to establish film as a mass art, which, hile still heavily politicized, no longer needs to call itself ‘African’, or ‘Arabic’ or ‘non-western’, fter all. Post-Third Cinema may therefore be a paradigm of multiplicity within World Cinema that is based n an emphatically universal approach. Regarded this way, it is an art form that is universal to the extent that it achieves a global appeal that transcends cultural differences. Drawing on the epistemology of multiplicity, as in recent times laid out by scholars such as Alain Badiou, Fredric Jameson or Quentin eillassoux, this article maps Post-Third Cinema as a paradigm of a media culture of multiplicity, ocusing on the idea of a cinematic epistemology that possesses a unique capacity for thought on its own.
Cinema is a country: The transgressive power of images in The Sea is Behind by Hicham Lasri
Authors: Fendler Ute 
Published: March 2020

Abstract
Since 2013, the Moroccan filmmaker Hicham Lasri has released a film each year, each of which has met with success at international festivals. All of these films transgress narrative and aesthetic cinematic boundaries, and is no exception: in a fable about the relations between human beings in a society that is losing its ethical and moral orientations, it invites us to consider our perception of the Other. The first part of the article addresses the active construction of its narrative from narrative fragments; the second part focuses on the ways in which the film's fragmented/composite narrative structure is reinforced by aesthetic means, so that, as the complex theme of the position and perception of marginalized groups is developed, new perspectives open up at the interstices, creating an impression of the dehumanizing conditions of life in this society.
The Underside of Power (Algiers): On W/Hole people, missing masses and dispositions of politics in popular cinema
Authors: Robnik Drehli 
Published: March 2020

Abstract
This article explores the relationships between popular film and politics of popular empowerment, especially in anti-colonial and anti-racist contexts. I am placing concepts from political theories in dialogic relationships with scenes from films. A basic tenet of this approach is that there is insight into movies, especially where orthodox scientific/philosophical discourses would not expect it (in genre cinemas, action film, horror movies, etc). So, my arguments are not made about films, but at their respective sites of insights. Conceptually, I take off first from the W/Hole of the people the popular as a totality necessarily haunted by incompleteness that figures in social struggles and dissensual film images; second, from the missing of masses as the people in an improper amount, a basic mistake in the counting of the social; and third, from dis-positions regarding power relations, also positionings on ‘sides’ (e.g., ‘undersides of power’) and on sites in social space, and dis-positioning in time, a.k.a. history.
Disequilibrium Trade in a Large Market for an Indivisible Good
Authors: Corchón Luis C. , Rueda-Llano José 
Published: March 2020

AbstractDisequilibrium trade can occur in a market lacking both recontracting and a computational system that maps utilities into prices. This paper studies disequilibrium trade in a large market for an indivisible good. We focus on the possible speed of adjustment when arbitrage among periods is feasible and the surplus loss. We find that incentive compatible sequential trade through a disequilibrium path is only compatible with sluggish price adjustments and sufficiently impatient agents. Thus, price adjustment does not depend on excess demand alone but on arbitrage opportunities and the willingness of agents to engage on them. We find that the upper bound on the speed of price adjustment involves a lower bound for the social surplus loss, whatever the kind of rationing. The reason is that even when the market price converges to the surplus maximizing value, as it happens when rationing is efficient, some pieces of surplus are not attainable at the current period due to arbitrage. Moreover, faster price adjustments do not imply less surplus loss, because the effect of price changes on transactions via arbitrage. Finally, under weaker-than-efficient rationing there is a one period incentive compatible trading procedure in which most of the surplus is destroyed. The procedure has the property that almost every agent in the market trades.
Identification of a four-gene methylation biomarker panel in high-grade serous ovarian carcinoma
Authors: Baranova Ivana , Kovarikova Helena , Laco Jan , Sedlakova Iva , Vrbacky Filip , Kovarik Dalibor , Hejna Petr , Palicka Vladimir , Chmelarova Marcela 
Published: March 2020

Abstract

Background
The lack of effective biomarkers for the screening and early detection of ovarian cancer (OC) is one of the most pressing problems in oncogynecology. Because epigenetic alterations occur early in the cancer development, they provide great potential to serve as such biomarkers. In our study, we investigated a potential of a four-gene methylation panel (including CDH13, HNF1B, PCDH17 and GATA4 genes) for the early detection of high-grade serous ovarian carcinoma (HGSOC).

Methods
For methylation detection we used methylation sensitive high-resolution melting analysis and real-time methylation specific analysis. We also investigated the relation between gene hypermethylation and gene relative expression using the 2−ΔΔCt method.

Results
The sensitivity of the examined panel reached 88.5%. We were able to detect methylation in 85.7% (12/14) of early stage tumors and in 89.4% (42/47) of late stage tumors. The total efficiency of the panel was 94.4% and negative predictive value reached 90.0%. The specificity and positive predictive value achieved 100% rates. Our results showed lower gene expression in the tumor samples in comparison to control samples. The more pronounced downregulation was measured in the group of samples with detected methylation.

Conclusions
In our study we designed the four-gene panel for HGSOC detection in ovarian tissue with 100% specificity and sensitivity of 88.5%. The next challenge is translation of the findings to the less invasive source for biomarker examination, such as plasma. Our results indicate that combination of examined genes deserve consideration for further testing in clinical molecular diagnosis of HGSOC.
The Disruptive Effect of Distributed Ledger Technology and Blockchain in the over the Counter Derivatives Market
Authors: Paolini Adolfo 
Published: March 2020

Abstract
The market for derivatives is substantially different after the 2007/08 financial crisis. Trust fuels business yet the financial crisis undermined this concept and customers lost faith in financial institutions. The then dichotomy, faced by innovators, was to insist with a system based on trust in financial institutions, or explore others where neither trust nor banks, as intermediaries, were indispensable for the successful and safe completion of financial transactions. The aim of this piece of research is to analyse to what extent innovative technology would change the way the ‘Over The Counter’ (OTC) market operates by providing investors with a trustworthy platform for the efficient assessment of the risk behind certain financial instruments. Consequently, the market may not be caught by surprise when another financial crisis strikes.
Chaotic Synchronization of Mutually Coupled Lasers with Another Laser and Its Encoding Application in Secret Communication
Authors: Senlin Yan 
Published: March 2020

Abstract
A chaotic synchronization based on mutually coupled different semiconductor lasers and its coding communications are studied. A route to chaos is illustrated by a bifurcate diagram. Chaotic distribution is presented in two lasers. The synchronization equation is given in theory. A chaotic synchronization is obtained between the emitter and the receiver. Other complex dynamical behavior synchronizations are also obtained, such as period-5 and period-10 synchronizations. Cascade synchronizations are achieved. A novel On/Off coding system is presented while its chaotic phase encoding is successfully implemented. Chaos key is also numerically simulated. We find that synchronization can still be achieved when the parameter of the emitter changes at any time so that the newly generated chaotic carrier can ensure mask the information in each communication. Then the real-time variable parameter results in difficulty for eavesdroppers to decipher. Compared with a single laser emitter, this emitter has many secret keys and high security, which is beneficial to its potential application in secret communication.
Diffraction-limited axial double foci and optical traps generated by optimization-free planar lens
Authors: Ma Long , Guan Jian , Wang Yiqun , Chen Chen , Zhang Jianlong , Lin Jie , Tan Jiubin , Jin Peng 
Published: March 2020

Abstract
Axial diffraction-limited multiple foci are a kind of investigated focal field for trapping multiple nano-particles. We first experimentally generated diffraction-limited axial double foci by optimization-free binary planar lens and theoretically demonstrated it, which can be applied in multi-particle trapping. The proposed binary planar lens was analytically designed. The BPL has a numerical aperture of 0.9 and a focal length of 150 μm. The focal field of the binary planar lens, which is composed of diffraction-limited axial double foci, was first experimentally validated. The measured maximum lateral full widths at half maximum of the two generated focal spots were diffraction-limited and consistent with the theoretical. The axial double foci formed two stable optical traps that can trap two Rayleigh dielectric particles simultaneously. The radial, azimuthal and axial optical forces of the double optical traps are in good uniformity, which are 0.98, 0.99 and 0.96, respectively.
Opto-thermoelectric speckle tweezers
Authors: Kotnala Abhay , Kollipara Pavana Siddhartha , Zheng Yuebing 
Published: March 2020

Abstract
Opto-thermoelectric tweezers present a new paradigm for optical trapping and manipulation of particles using low-power and simple optics. New real-life applications of opto-thermoelectric tweezers in areas such as biophysics, microfluidics, and nanomanufacturing will require them to have large-scale and high-throughput manipulation capabilities in complex environments. Here, we present opto-thermoelectric speckle tweezers, which use speckle field consisting of many randomly distributed thermal hotspots that arise from an optical speckle pattern to trap multiple particles over large areas. By further integrating the speckle tweezers with a microfluidic system, we experimentally demonstrate their application for size-based nanoparticle filtration. With their low-power operation, simplicity, and versatility, opto-thermoelectric speckle tweezers will broaden the applications of optical manipulation techniques.
Novel two-dimensional monoelemental and ternary materials: growth, physics and application
Authors: Gao Wei , Zheng Zhaoqiang , Wen Peiting , Huo Nengjie , Li Jingbo 
Published: March 2020

Abstract
Two-dimensional (2D) materials have undergone a rapid development toward real applications since the discovery of graphene. At first, graphene is a star material because of the ultrahigh mobility and novel physics, but it always suffered from zero bandgap and limited device application. Then, 2D binary compounds such as transition-metal chalcogenides emerged as complementary materials for graphene due to their sizable bandgap and moderate electrical properties. Recently, research interests have turned to monoelemental and ternary 2D materials. Among them, monoelemental 2D materials such as arsenic (As), antimony (Sb), bismuth (Bi), tellurium (Te), etc., have been the focus. For example, bismuthene can act as a 2D topological insulator with nontrivial topological edge states and high bulk gap, providing the novel platforms to realize the quantum spin-Hall systems. Meanwhile, ternary 2D materials such as Bi2O2Se, BiOX and CrOX (X=Cl, Br, I) have also emerged as promising candidates in optoelectronics and spintronics due to their extraordinary mobility, favorable band structures and intrinsic ferromagnetism with high Curie temperature. In this review, we will discuss the recent works and future prospects on the emerging monoelemental and ternary materials in terms of their structure, growth, physics and device applications.