bluuebunny/crossref_metadata_2025 huggingface dataset:
Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina
Authors: Bertoli Hanna Kristina , Rasmussen Christina Louise , Sand Freja Lærke , Albieri Vanna , Norrild Bodil , Verdoodt Freija , Kjaer Susanne K.
Published: December 2018

We estimated the overall and type‐specific prevalence of human papillomavirus (HPV) and p16 overexpression in vaginal cancer and vaginal intraepithelial neoplasia (VaIN). We conducted a systematic search of PubMed, Embase and Cochrane Library to identify studies published between 1986 and 2017 using PCR‐based or Hybrid Capture 2 tests to evaluate the presence of HPV DNA and/or using any method to detect p16 overexpression in VaIN, vaginal squamous cell carcinoma (VaSCC), or other types of vaginal cancer. Applying a random effects model, we estimated the pooled prevalence of HPV and p16 overexpression along with 95% confidence intervals (CIs). The I2 statistic was used to assess heterogeneity. We included 26 studies, reporting HPV prevalence and six studies evaluating p16 overexpression. The pooled HPV prevalences in VaSCC (n = 593) and VaIN (n = 1,374) were 66.7% (95% CI = 54.7–77.8) and 85.2% (95% CI = 78.2–91.0), respectively. Substantial inter‐study heterogeneity was observed, and analyses stratified on geographic region, type of tissue, HPV detection method or PCR primer type did not fully explain the observed heterogeneity. The most predominant HPV type among the HPV positive VaSCC and VaIN cases was HPV16, followed by HPV33, and HPV45 (in VaIN) and HPV18, and HPV33 (in VaSCC). In pooled analyses, 89.9% (95% CI = 81.7–94.6) of HPV positive and 38.9% (95% CI = 0.9–90.0) of HPV negative vaginal cancers were positive for p16 overexpression. Our findings suggest that vaccination against HPV might prevent a substantial proportion of vaginal neoplasia and highlight the need for further studies of the possible clinical value of p16 testing in these patients.
Bladder cancer metastasis producing beta‐human chorionic gonadotropin, squamous cell carcinoma antigen, granulocyte‐colony stimulating factor, and parathyroid hormone‐related protein
Authors: Hoshi Senji , Numahata Kenji , Morozumi Kento , Katumata Yuuki , Kuromoto Akito , Takai Yuuki , Hoshi Kiyotugu , Bilim Vladimir , Sasagawa Isoji
Published: December 2018

Introduction

In urothelial cancer, several paraneoplastic syndromes can be triggered by the aberrant expression of hormones, growth factors or lymphokines by tumor cells.

Case presentation

A 71‐year‐old female patient underwent radical cystectomy for muscle‐invasive urothelial cancer. Shortly after the operation, the patient presented with a leukemoid reaction and hypercalcemia. Computed tomography scans revealed a rapidly progressing tumor on the left pelvic side, and serum levels of granulocyte‐colony stimulating factor, parathyroid hormone‐related protein, and beta human chorionic gonadotropin were elevated. The patient also tested positive for serum squamous cell carcinoma antigen. Hypercalcemia was successfully treated with denosumab. However, the patient's leukocyte counts steadily increased, her condition deteriorated and she passed away.

Conclusion

To the best of our knowledge, this is the first report of urothelial cancer that tested positive for four tumor markers. The findings support the idea that poorly differentiated bladder carcinomas can ectopically secrete multiple proteins causing pleiotropic paraneoplastic syndromes.
Urban Wet‐Weather Flows
Authors: Rangarajan Srinivasan , Sample David J. , Boone Matthew , Lee Joong , Muneer Alie , Narayanaswamy Karthik , Hochstedler Megan
Published: December 2018

This literature review summarizes significant technical literature published in 2010 and 2011 in the major areas of urban wet‐weather flows. The review covers a range of topics including characterization, pollution sources, monitoring and sampling, surface and groundwater impacts, mathematical modeling tools and decision support systems, regulatory policies, and control and treatment technologies. Some gaps in the literature compilation have also been identified and presented to support future research efforts.
Prenatal exposure to PCBs in Cyp1a2 knock‐out mice interferes with F1 fertility, impairs long‐term potentiation, reduces acoustic startle and impairs conditioned freezing contextual memory with minimal transgenerational effects
Authors: Hufgard Jillian R. , Sprowles Jenna L.N. , Pitzer Emily M. , Koch Sheryl E. , Jiang Min , Wang Qin , Zhang Xiang , Biesiada Jacek , Rubinstein Jack , Puga Alvaro , Williams Michael T. , Vorhees Charles V.
Published: December 2018

Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three‐coplanar/five‐noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2−/−::Ahrb1 C57BL6/J mice compared with wild‐type mice (Ahrb1 = high AHR affinity). Here we exposed gravid Cyp1a2−/−::Ahrb1 mice to a PCB mixture on embryonic day 10.5 by gavage and examined the F1 and F3 offspring (not F2). PCB‐exposed F1 mice exhibited increased open‐field central time, reduced acoustic startle, greater conditioned contextual freezing and reduced CA1 hippocampal long‐term potentiation with no change in spatial learning or memory. F1 mice also had inhibited growth, decreased heart rate and cardiac output, and impaired fertility. F3 mice showed few effects. Gene expression changes were primarily in F1 PCB males compared with wild‐type males. There were minimal RNA and DNA methylation changes in the hippocampus from F1 to F3 with no clear relevance to the functional effects. F0 PCB exposure during a period of rapid DNA de‐/remethylation in a susceptible genotype produced clear F1 effects with little evidence of transgenerational effects in the F3 generation. While PCBs show clear developmental neurotoxicity, their effects do not persist across generations for effects assessed herein.
MiR‐99a‐5p inhibits bladder cancer cell proliferation by directly targeting mammalian target of rapamycin and predicts patient survival
Authors: Liu Yan , Li Bingxun , Yang Xianxu , Zhang Chenglong
Published: December 2018

Bladder cancer is a common malignancy and miR‐99a‐5p has been reported to be downregulated in bladder cancer, but its function and the underlying mechanism in bladder cancer development remains largely unclear. Here, we report that miR‐99a‐5p expression was decreased in bladder cancer compared with the adjacent normal tissues. Receiver operating characteristic curve revealed that miR‐99a‐5p expression signature had area under curve value of 0.7989 in differing bladder cancer from the adjacent normal tissues. Bladder cancer patients with low expression of miR‐99a‐5p had a poor survival rate. Gain‐of‐function and loss‐of‐function approaches demonstrated that miR‐99a‐5p inhibited bladder cell proliferation and cell cycle. Furthermore, we identified that mammalian target of rapamycin (mTOR) was a direct target of miR‐99a‐5p and mTOR restore could rescue the proliferative ability of bladder cancer cells. Moreover, miR‐99a‐5p/mTOR axis regulated S6K1 phosphorylation. These suggested that miR‐99a‐5p/mTOR axis might be a therapeutic target for bladder cancer.
Dangerous, depraved, and death‐worthy: A meta‐analysis of the correlates of perceived psychopathy in jury simulation studies
Authors: Kelley Shannon E. , Edens John F. , Mowle Elyse N. , Penson Brittany N. , Rulseh Allison
Published: December 2018

Objectives

Experimental research suggests that legal defendants described as psychopathic are generally, although not uniformly, judged more negatively and punitively. Understanding the correlates of perceived psychopathy, regardless of exposure to mental health evidence, is an important step towards clarifying divergent findings.

Method

We conducted a quantitative synthesis of ten juror simulation studies (combined N = 2,980) examining the meta‐analytic association between perceived defendant psychopathy and various psychologically important and legally relevant outcomes.

Results

Perceiving someone as being more psychopathic was associated with viewing that defendant as more dangerous (r
W = 0.31) and evil (
r
W = 0.44). Moreover, perceptions of defendant psychopathy predicted greater support for more adverse consequences in terms of capital sentencing (
r
W = 0.22) and sentence length (
r
W = 0.27), although not perceived treatment amenability (
r
W = 0.09).

Conclusions

These findings highlight the importance of including ratings of perceived psychopathy in experimental designs to identify the circumstances under which psychopathy evidence might prejudicially impact case outcomes.
Characterization and visualization of the liposecretion process taking place during ceiling culture of human mature adipocytes
Authors: Côté Julie Anne , Gauthier Marie‐Frédérique , Ostinelli Giada , Brochu Dannick , Bellmann Kerstin , Marette André , Julien François , Lebel Stéfane , Tchernof André
Published: December 2018

Objective

To investigate and further characterize the process of mature adipocyte dedifferentiation. Our hypothesis was that dedifferentiation does not involve mitosis but rather a phenomenon of liposecretion.

Methods

Mature adipocytes were isolated by collagenase digestion of human adipose tissue samples. Ceiling cultures were established using our six‐well plate model. Cells were treated with cytosine β‐d‐arabinofuranoside (AraC) or vincristine (VCR), two agents blocking cell division, and were compared with vehicle. Liposecretion events were visualized by time‐lapse microscopy, with and without AraC in adipocytes transducted with a baculovirus. Microscopic analyses were performed after labeling phosphorylated histone 3 and cyclin B1 in ceiling cultures.

Results

Treatment with AraC almost entirely prevented the formation of fibroblasts up to 12 days of ceiling culture. Similar results were obtained with VCR. The antimitotic effectiveness of the treatment was confirmed in fibroblast cultures from the adipose tissue stromal‐vascular fraction by proliferation assays and colony‐forming unit experiments. Using time‐lapse microscopy, we visualized liposecretion events in which a large lipid droplet was rapidly secreted from isolated mature adipocytes. The same phenomenon was observed with AraC. This was observed in conjunction with histone 3 phosphorylation and cyclin B1 segregation to the nucleus.

Conclusion

Our results support the notion that dedifferentiation involves rapid secretion of the lipid droplet by the adipocytes with concomitant generation of fibroblast‐like cells that subsequently proliferate to generate the dedifferentiated adipocyte population during ceiling culture. The presence of mitotic markers suggests that this process involves cell cycle progression, although cell division does not occur.
On the (Non‐)equivalency of monopolar and bipolar settings for deep brain stimulation fMRI studies of Parkinson's disease patients
Authors: Hancu Ileana , Boutet Alexandre , Fiveland Eric , Ranjan Manish , Prusik Julia , Dimarzio Marisa , Rashid Tanweer , Ashe Jeffrey , Xu David , Kalia Suneil K. , Hodaie Mojgan , Fasano Alfonso , Kucharczyk Walter , Pilitsis Julie , Lozano Andres , Madhavan Radhika
Published: December 2018

Background

The majority of Parkinson's disease patients with deep brain stimulation (DBS) use a monopolar configuration, which presents challenges for EEG and MRI studies. The literature reports algorithms to convert monopolar to bipolar settings.

Purpose/Hypothesis

To assess brain responses of Parkinson's disease patients implanted with DBS during fMRI studies using their clinical and presumed equivalent settings using a published conversion recipe.

Study Type

Prospective.

Subjects

Thirteen DBS patients.

Field Strength/Sequence

1.5T and 3T, fMRI using gradient echo‐planar imaging.

Assessment

Patients underwent 30/30sec ON/OFF DBS fMRI scans using monopolar and bipolar settings. To convert to a bipolar setting, the negative contact used for the monopolar configuration remained constant and the adjacent dorsal contact was rendered positive, while increasing the voltage by 30%. fMRI activation/deactivation maps and motor Unified Parkinson's Disease Rating Scale (UPDRS‐III) scores were compared for patients in both configurations.

Statistical Tests

T‐tests were used to compare UPDRS scores and volumes of tissue activated (VTA) diameters in monopolar and bipolar configurations.

Results

The patterns of fMRI activation in the monopolar and bipolar configurations were generally different. The thalamus, pallidum, and visual cortices exhibited higher activation using the patient's clinical settings than the presumed equivalent settings. VTA diameters were lower (7 mm vs. 6.3 mm, P = 0.047) and UPDRS scores were generally higher in the bipolar (33.2 ± 16) than in the monopolar configuration (28.3 ± 17.4), without reaching statistical significance (P > 0.05).

Data Conclusion

Monopolar and bipolar configurations result in different patterns of brain activation while using a previously published monopolar–bipolar conversion algorithm. Clinical benefits may be achieved with varying patterns of brain responses. Blind conversion from one to the other should be avoided for purposes of understanding the mechanisms of DBS.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018.
The evolution and molecular characteristics of H9N2 avian influenza viruses in Jiangxi of China
Authors: Han Le , He Weijun , Yan Huixin , Li Xianglan , Wang Chengmin , Shi Qiumei , Zhou Tiezhong , Dong Guoying
Published: December 2018

To understand the evolution and molecular characteristics of Jiangxi H9N2 viruses, we isolated 17 viruses in 2011 and analyzed their characteristics. Phylogenetic analyses revealed that their hemagglutinin genes originate from JS/1/00‐like sublineage, neuraminidase genes originate from BJ/94‐like sublineage, PB1, PA, NP, and NS genes all come from SH/F/98‐like sublineage, PB2 genes originate from ST/163/04‐like sublineage, while M genes come from G1‐like sublineage. Genotype analysis showed that our isolates were classified as genotype 57. Molecular analyses indicated that our strains contained specific sites characteristic of low‐pathogenic viruses. The current study once again highlights the necessity for continued surveillance of novel H9N2 viruses.
Indications for the surgical resection of stage IV disease
Authors: Bello Danielle M.
Published: December 2018

Tumor biology and careful patient selection weigh heavily in determining the appropriate role of surgical resection in stage IV melanoma. Historically, surgical resection for highly selected patients with metastatic melanoma was the only treatment modality associated with improved long‐term survival and the ability to provide palliation. With the new age of effective systemic therapies, the treatment of metastatic melanoma has become more intricate and future work is needed to better define the role for surgery within the current treatment paradigm.
Novel Quantitative Contrast‐Enhanced Ultrasound Detection of Hypoxic Ischemic Injury in Neonates and Infants: Pilot Study 1
Authors: Hwang Misun , Sridharan Anush , Darge Kassa , Riggs Becky , Sehgal Chandra , Flibotte John , Huisman Thierry A. G. M.
Published: December 2018

Objectives

To investigate whether quantitative contrast‐enhanced ultrasound (CEUS) can accurately identify neonates and infants with hypoxic ischemic brain injury.

Methods

In this prospective cohort study, 8 neonates and infants with a suspicion of hypoxic ischemic injury were evaluated with CEUS.

Results

An interesting trend was observed in the central gray nuclei–to–cortex perfusion ratios. The ratios at the peak enhancement, wash‐in area under the curve, perfusion index, and maximum wash‐in slopes were lower in all of the affected cases compared to the normal group but not statistically significant given the small sample size (P = .0571). Additionally, when the central gray nuclei–to–cortex perfusion ratio was plotted for all time points along the time‐intensity curve, it was observed that the affected cases showed a trend that was qualitatively different from that of the normal cases. In the affected cases, the ratio time‐intensity curves either stayed below 1.0 for the entire enhancement period or reached 1.0 close to peak wash‐in before falling just below 1.0 for the remaining period of enhancement. However, in the unaffected patients, there was a steep wash‐in that crossed the 1.0 threshold and remained above 1.0 for most of the enhancement period.

Conclusions

Bedside CEUS is an easily obtainable brain‐imaging modality that has the potential to effectively identify infants and neonates with evolving brain injury. A larger prospective study evaluating the correlation between CEUS findings and the reference standard of diffusion‐ and perfusion‐weighted magnetic resonance imaging is needed to establish it as a diagnostic tool.
Long‐term perspectives in aquatic research
Authors: Hampton Stephanie E. , Scheuerell Mark D. , Church Matthew J. , Melack John M.
Published: December 2018

Abstract

Long‐term research provides a unique perspective on environmental processes, dynamics of populations and communities of organisms, and emergent properties of ecosystems. Many key ecological relationships can be obscured in short term studies by common features such as time lags, natural variability, nonlinear relationships, interactive drivers, or relatively slow processes. Aquatic ecosystems have yielded major scientific discoveries through long‐term research, through both observational and experimental studies. These research results have ranged from the detection of multi‐decadal climate oscillation effects on ecosystems to finer‐scale understanding of the trophic and biogeochemical pathways through which nutrient pollution affects water quality. In this special issue of Limnology and Oceanography, the contributing authors demonstrate that—whether designed for the monitoring of managed natural resources, to answer fundamental scientific questions, or both—long‐term research enables researchers to move far beyond their initial questions as unexpected dynamics are revealed over time. With the widespread maturation of long‐term data sets and rapid emergence of new technologies that enhance research capabilities, opportunities for synthesizing knowledge are now creating unprecedented opportunity for scientific discovery that builds on this legacy of long‐term aquatic research.
Fabrication and Application of Highly Stretchable Conductive Fiber‐Based Electrode of Epoxy/NBR Electrospun Fibers Spray‐Coated with AgNW/PU Composites
Authors: Liu Hsin‐Yu , Hsieh Hui‐Ching , Chen Jung‐Yao , Shih Chien‐Chung , Lee Wen‐Ya , Chiang Yun‐Chi , Chen Wen‐Chang
Published: December 2018

Stretchable fiber‐based electrodes are highly desired for the applications of wearable electronics owing to their good durability, excellent deformability, and easy attachment onto a curved surface in comparison with thin film electrodes. However, it is a critical challenge to fabricate a fiber‐based electrodes with low surface roughness and high conductivity under a large mechanical strain. In this study, the fabrication of stretchable and conductive epoxy/NBR‐20 fiber, spray‐coated with silver nanowire/waterborne polyurethane composite, is demonstrated via the combination of electrospinning and spray‐coating techniques. Such a fiber‐based electrode can maintain low resistance (less than 150 Ω) by stretching up to 40% strain and sustain at 30% strain for 200 stretch/release cycles. The deformable conductive fibers can serve as a promising fiber‐based bottom electrode for resistive memory devices and show volatile DRAM characteristics with an ON/OFF memory ratio of 102.
Consumer Brand Hate: Steam rolling whatever I see
Authors: Kucuk S. Umit
Published: December 2018

This study aims to investigate negative consumer‐brand relationships by developing a “Brand Hate” concept. A hierarchical Brand Hate model is theoretically discussed in light of the psychology and consumer behavior literatures. In Study‐I the Brand Hate concept was tested with two different types of consumer brand haters, true haters, and regular haters. The study found that in the study's proposed multidimensional Brand Hate hierarchy true haters display “Boiling Brand Hate” while regular haters reveal “Seething Brand Hate.” Two additional studies were developed to examine the relationship between consumer personality traits and Brand Hate, exploring which types of consumers are more prone to feel hatred toward targeted brands. Study‐II's findings revealed a relationship between consumers who are high in personality traits of “conscientiousness” and those who Brand Hate. Study‐III's findings indicated that “self‐confident” and “competitive” consumers might also be more prone to feel hatred toward those brands that perform poorly and unethically.
Cholera model incorporating media coverage with multiple delays
Authors: Liao Shu , Yang Weiming
Published: December 2018

In order to investigate the impact of awareness programs and time delays on the cholera outbreaks, we propose a cholera epidemic model, incorporating awareness programs by media as a separate class and two time‐delay factors. The bifurcation theory is applied to explore the variety of dynamics of this model for various combinations of the delays when R0>1. Moreover, we analyze the direction, stability, and period of the bifurcating periodic solutions arising through Hopf bifurcation by using the normal form concept and the center manifold theory. Finally, we present numerical simulations to verify the main theoretical results.
Simultaneous multislice cardiac magnetic resonance fingerprinting using low rank reconstruction
Authors: Hamilton Jesse I. , Jiang Yun , Ma Dan , Chen Yong , Lo Wei‐Ching , Griswold Mark , Seiberlich Nicole
Published: December 2018

This study introduces a technique for simultaneous multislice (SMS) cardiac magnetic resonance fingerprinting (cMRF), which improves the slice coverage when quantifying myocardial T1, T2, and M0. The single‐slice cMRF pulse sequence was modified to use multiband (MB) RF pulses for SMS imaging. Different RF phase schedules were used to excite each slice, similar to POMP or CAIPIRINHA, which imparts tissues with a distinguishable and slice‐specific magnetization evolution over time. Because of the high net acceleration factor (R = 48 in plane combined with the slice acceleration), images were first reconstructed with a low rank technique before matching data to a dictionary of signal timecourses generated by a Bloch equation simulation. The proposed method was tested in simulations with a numerical relaxation phantom. Phantom and in vivo cardiac scans of 10 healthy volunteers were also performed at 3 T. With single‐slice acquisitions, the mean relaxation times obtained using the low rank cMRF reconstruction agree with reference values. The low rank method improves the precision in T1 and T2 for both single‐slice and SMS cMRF, and it enables the acquisition of maps with fewer artifacts when using SMS cMRF at higher MB factors. With this technique, in vivo cardiac maps were acquired from three slices simultaneously during a breathhold lasting 16 heartbeats. SMS cMRF improves the efficiency and slice coverage of myocardial T1 and T2 mapping compared with both single‐slice cMRF and conventional cardiac mapping sequences. Thus, this technique is a first step toward whole‐heart simultaneous T1 and T2 quantification with cMRF.
Minimum‐risk routing through a mapped minefield
Authors: Richards Christopher , Odom Christopher , Morton David , Newman Alexandra
Published: December 2018

We embed a directed graph G(V, E) in a representation of a naval minefield; vertices V represent waypoints and edges E denote possible segments for ship transit. A new model identifies a simple s‐t path through the minefield that minimizes the risk of incurring unacceptable damage from threats, that is, mine detonations. Traditional “edge‐additive” models rely on shortest‐path algorithms that over‐accumulate risk along a path. Our “threat‐additive” approach accumulates risk based upon the path's closest point of approach to each mine. We formulate and solve this model (1) using an integer program (IP) and its stronger variant, and (2) via an A* search algorithm. Preprocessing routines are key to reducing run times. We investigate the relative merits, both with respect to solution quality and requisite computational effort, of two types of graphs, one based on a rectilinear scheme and one based on Voronoi diagrams. We find that graphs based on Voronoi diagrams provide higher quality solutions with less computational effort, and that the A* search procedure requires less computational effort than solving instances of our models as IPs.
Deep convolutional neural networks for eigenvalue problems in mechanics
Authors: Finol David , Lu Yan , Mahadevan Vijay , Srivastava Ankit
Published: December 2018

We show that deep convolutional neural networks (CNNs) can massively outperform traditional densely connected neural networks (NNs) (both deep or shallow) in predicting eigenvalue problems in mechanics. In this sense, we strike out in a new direction in mechanics computations with strongly predictive NNs whose success depends not only on architectures being deep but also being fundamentally different from the widely used to date. We consider a model problem: predicting the eigenvalues of one‐dimensional (1D) and two‐dimensional (2D) phononic crystals. For the 1D case, the optimal CNN architecture reaches 98% accuracy level on unseen data when trained with just 20 000 samples, compared to 85% accuracy even with 100 000 samples for the typical network of choice in mechanics research. We show that, with relatively high data efficiency, CNNs have the capability to generalize well and automatically learn deep symmetry operations, easily extending to higher dimensions and our 2D case. Most importantly, we show how CNNs can naturally represent mechanical material tensors, with its convolution kernels serving as local receptive fields, which is a natural representation of mechanical response. Strategies proposed are applicable to other mechanics' problems and may, in the future, be used to sidestep cumbersome algorithms with purely data‐driven approaches based upon modern deep architectures.
Flow‐cytometric minimal residual disease monitoring in blood predicts relapse risk in pediatric B‐cell precursor acute lymphoblastic leukemia in trial AIEOP‐BFM‐ALL 2000
Authors: Schumich Angela , Maurer‐Granofszky Margarita , Attarbaschi Andishe , Pötschger Ulrike , Buldini Barbara , Gaipa Giuseppe , Karawajew Leonid , Printz Dieter , Ratei Richard , Conter Valentino , Schrappe Martin , Mann Georg , Basso Giuseppe , Dworzak Michael N. ,   AIEOP‐BFM‐ALL‐FLOW‐Study Group
Published: December 2018

Background

Flow‐cytometric monitoring of minimal residual disease (MRD) in bone marrow (BM) during induction of pediatric patients with acute lymphoblastic leukemia (ALL) is widely used for outcome prognostication and treatment stratification. Utilizing peripheral blood (PB) instead of BM might be favorable, but data on its usefulness are scarce.

Procedure

We investigated 1303 PB samples (days 0, 8, 15, 33, and 52) and 285 BMs (day 15) from 288 pediatric ALL patients treated in trial AIEOP‐BFM ALL 2000. MRD was assessed by four‐color flow cytometry and evaluated as relative, absolute, and kinetic result.

Results

In B‐ALL only, PB measures from early time points correlated with relapse incidence (CIR). Best separation occurred at threshold <1 blast/μL at day 8 (5‐year CIR 0.02 ± 0.02 vs 0.12 ± 0.03;P = 0.044). Patients with highest relapse risk were not distinguishable, but PB‐MRD at days 33 and 52 correlated with prednisone response and postinduction BM‐MRD by PCR (P < 0.001). Kinetic assessment did not convey any advantage. In multivariate analysis including day 15 BM‐MRD, PB‐MRD measures lost statistical power.

Conclusions

In summary, PB‐MRD in pediatric B‐ALL correlates with outcome and risk parameters, but its prognostic significance is not strong enough to substitute for BM assessment in AIEOP‐BFM trials. It might, however, be valuable in treatment environments not using multifaceted risk stratification with other MRD measures.
Photocrosslinkable chitosan hydrogels and their biomedical applications
Authors: Pei Minjie , Mao Jun , Xu Weilin , Zhou Yingshan , Xiao Pu
Published: December 2018

Chitosan is a bioactive macromolecule with a wide variety of applications due to its excellent biological properties such as biodegradability, biocompatibility, and antibacterial activity, and so forth. This highlight focuses on the preparation of photoactive chitosans, the formation of photocrosslinkable chitosan hydrogels, and the related photopolymerization mechanisms. Moreover, the great potential applications of photocrosslinkable chitosan hydrogels for human tissues are also discussed. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1862–1871
Continuous Synthesis of Cyclohexene Oxide in a Micro‐FlowSystem
Authors: Zhou Yu , He Wei , Fang Zheng , Guo Kai
Published: December 2018

Epoxidation reaction catalyzed by dicyclohexylcarbodiimide(DCC) was realized in a microflow system, resulting in cyclohexene oxide with high yields. In this study, the epoxidation process of cyclohexene in MFS was investigated in detail. The optimal yield was obtained in such conditions: temperature 80°C, residence time 12 min, catalyst concentration 3%, ratio of cyclohexene to UHP 1:8. Basic additions played an important role in the collapse of adducts.
Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications
Authors: Jiang Bin , Yan Li , Wang Xiaoyan , Li Enqin , Murphy Kyle , Vaccaro Kyle , Li Yingcui , Xu Ren-He
Published: December 2018

Despite the long discrepancy over their definition, heterogeneity, and functions, mesenchymal stem cells (MSCs) have proved to be a key player in tissue repair and homeostasis. Generally, somatic tissue-derived MSCs (st-MSCs) are subject to quality variations related to donated samples and biosafety concern for transmission of potential pathogens from the donors. In contrast, human pluripotent stem cells (hPSCs) are unlimited in supply, clear in the biological background, and convenient for quality control, genetic modification, and scale-up production. We, and others, have shown that hPSCs can differentiate in two dimensions or three dimensions to MSCs (ps-MSCs) via embryonic (mesoderm and neural crest) or extraembryonic (trophoblast) cell types under serum-containing or xeno-free and defined conditions. Compared to st-MSCs, ps-MSCs appear less mature, proliferate faster, express lower levels of inflammatory cytokines, and respond less to traditional protocols for st-MSC differentiation to other cell types, especially adipocytes. Nevertheless, ps-MSCs are capable of immune modulation and treatment of an increasing number of animal disease models via mitochondria transfer, paracrine, exosomes, and direct differentiation, and can be potentially used as a universal and endless therapy for clinical application. This review summarizes the progress on ps-MSCs and discusses perspectives and challenges for their potential translation to the clinic. Stem Cells  2019;37:572–581
J/ψ polarization in the CGC+NRQCD approach
Authors: Ma Yan-Qing , Stebel Tomasz , Venugopalan Raju
Published: December 2018

Abstract

We compute the J/ψ polarization observables λ

θ
, λ

ϕ
, λ

θϕ
in a Color Glass Condensate (CGC) + nonrelativistic QCQ (NRQCD) formalism that includes contributions from both color singlet and color octet intermediate states. Our results are compared to low p

T
data on J/ψ polarization from the LHCb and ALICE experiments on proton-proton collisions at center-of-mass energies of

$$ \sqrt{s}=7 $$

s

=
7

TeV and 8 TeV. Our CGC+NRQCD computation provides a better description of data for p

T
≤ 15 GeV relative to extant next-to-leading (NLO) calculations within the collinear factorization framework. These results suggest that higher order computations in the CGC+NRQCD framework have the potential to greatly improve the accuracy of extracted values of the NRQCD universal long distance matrix elements.
The Smeared Null Energy Condition
Authors: Freivogel Ben , Krommydas Dimitrios
Published: December 2018

Abstract

We propose a new bound on a weighted average of the null energy along a finite portion of a null geodesic: the Smeared Null Energy Condition (SNEC). We believe our bound is valid on scales small compared to the radius of curvature in any quantum field theory that is consistently coupled to gravity. If correct, our bound implies that regions of negative energy density are never strongly gravitating, and that isolated regions of negative energy are forbidden.
What do gravitons say about (unimodular) gravity?
Authors: Herrero-Valea Mario
Published: December 2018

Abstract

We revisit the problem of constraining the weak field limit of the gravitational lagrangian from S-matrix properties. From unitarity and Lorentz invariance of the S-matrix of massless gravitons, we derive on-shell gauge invariance to consist on the transverse part of the linearised diffeomorphisms group. Moreover, by looking to the interaction between sources, we conclude that there exist only two possible lagrangians that lead to a welldefined covariant interaction, corresponding to the weak field limits of General Relativity and Unimodular Gravity. Additionally, this result confirms the equivalence of the S-matrix of both theories around flat space-time.
VASC: Dimension Reduction and Visualization of Single-Cell RNA-Seq Data by Deep Variational Autoencoder
Authors: Wang Dongfang , Gu Jin
Published: December 2018

Single-cell RNA sequencing (scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell sub-populations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data (VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.
Preparing to launch the ‘Thinking Healthy Programme’ perinatal depression intervention in Urban Lima, Peru: experiences from the field
Authors: Eappen B. S. , Aguilar M. , Ramos K. , Contreras C. , Prom M. C. , Scorza P. , Gelaye B. , Rondon M. , Raviola G. , Galea J. T.
Published: December 2018

Background.

An estimated 19–25% of perinatal women in low- and middle-income countries are affected by depression which, untreated, is associated with multiple health problems for mothers and children. Nonetheless, few perinatal women have access to depression care. The Thinking Healthy Programme (THP), promoted by the World Health Organization (WHO), is an evidence-based, non-specialist delivered depression intervention that addresses this care gap. However, the WHO THP manual explains intervention delivery but not the antecedents to implementation. Here, we describe a principled, planned approach leading to the implementation of THP in Lima, Peru by the non-profit organization Socios En Salud with community health workers (CHW) to inform its implementation in other settings.

Methods.

The Replicating Effective Programs (REP) framework guided THP implementation, following four phases: (I) pre-conditions; (II) pre-implementation; (III) implementation; and (IV) maintenance and evolution. This paper centers on REP phases I and II, including (1) documented high perinatal depression rates in Peru; (2) designation of perinatal depression as a government priority; (3) THP Implementation Team orientation and training; (4) data collection plan development; (5) public health system coordination; (6) CHW selection and training; and (7) THP launch.

Results.

Between December 2016 and March 2017, a THP training program was developed and seven CHW were trained to deliver the intervention to 10 perinatal women, the first of whom was enrolled on 17 April 2017.

Conclusions.

THP was rapidly implemented by a community-based organization with no prior experience in delivering non-specialist perinatal depression care. The steps followed may inform the implementation of THP in other settings.
Optimization of the pulse width and injection time in a double-pass laser amplifier
Authors: Park Daewoong , Jeong Jihoon , Yu Tae Jun
Published: December 2018

We have optimized the input pulse width and injection time to achieve the highest possible output pulse energy in a double-pass laser amplifier using two Nd:YAG rods. For this purpose, we have extended the Frantz–Nodvik equation by simultaneously including both spontaneous emission and pump energy variation. The effective pump energy of the flash lamp was 8.84 J for each gain medium. The energy of 1 J could be amplified to an output energy of 12.17 J with the maximum achieved extraction efficiency of 63.18% when an input pulse having a pulse width of 168 $\unicode[STIX]{x03BC}$s is sent 10 $\unicode[STIX]{x03BC}$s after the absorbed pump energy becomes the maximum value.
Patient isolation for infection control and patient experience
Authors: Siddiqui Zishan K. , Conway Sarah Johnson , Abusamaan Mohammed , Bertram Amanda , Berry Stephen A. , Allen Lisa , Apfel Ariella , Farley Holley , Zhu Junya , Wu Albert W. , Brotman Daniel J.
Published: December 2018

Objective

Hospitalized patients placed in isolation due to a carrier state or infection with resistant or highly communicable organisms report higher rates of anxiety and loneliness and have fewer physician encounters, room entries, and vital sign records. We hypothesized that isolation status might adversely impact patient experience as reported through Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, particularly regarding communication.

Design

Retrospective analysis of HCAHPS survey results over 5 years.

Setting

A 1,165-bed, tertiary-care, academic medical center.

Patients

Patients on any type of isolation for at least 50% of their stay were the exposure group. Those never in isolation served as controls.

Methods

Multivariable logistic regression, adjusting for age, race, gender, payer, severity of illness, length of stay and clinical service were used to examine associations between isolation status and “top-box” experience scores. Dose response to increasing percentage of days in isolation was also analyzed.

Results

Patients in isolation reported worse experience, primarily with staff responsiveness (help toileting 63% vs 51%; adjusted odds ratio [aOR], 0.77; P = .0009) and overall care (rate hospital 80% vs 73%; aOR, 0.78; P < .0001), but they reported similar experience in other domains. No dose-response effect was observed.

Conclusion

Isolated patients do not report adverse experience for most aspects of provider communication regarded to be among the most important elements for safety and quality of care. However, patients in isolation had worse experiences with staff responsiveness for time-sensitive needs. The absence of a dose-response effect suggests that isolation status may be a marker for other factors, such as illness severity. Regardless, hospitals should emphasize timely staff response for this population.
What makes a team brilliant? An experiential exploration of positivity within healthcare
Authors: Fulop Emeritus Liz , Kippist Louise , Dadich Ann , Hayes Kate , Karimi Leila , Symth Anne
Published: December 2018

Following its positive outcomes in a state-wide survey, co-managers of the Queensland Cancer Control Analysis Team commissioned discovery interviews to explore these results. Eleven interviews were analysed by positive organisational scholars who drew on depreciating and appreciating organisational dynamics to make sense of Queensland Cancer Control Analysis Team’s high performance. An initial framework was devised, including appreciative, depreciative, and hybrid dynamics, with the latter representing an extension to an existing taxonomy. Findings revealed mainly appreciative and hybrid dynamics. To further understand these, the framework was expanded by reframing the dynamics as positive institutional work. This extension offers an experiential understanding of positive institutional patterns by incorporating the troika of experiential surfacing, agency as inquiry, and inclusion. The value of this framework is threefold, for it can be used as an analytic, a diagnostic, and an intervention tool to enable scholars and practitioners to operationalise positive organisational scholarship to examine, understand, and promote positive organisational experiences.
The case for replicable structured full proportionality analysis in all cases concerning fundamental rights
Authors: Ramshaw Adam
Published: December 2018

Proportionality has been testing the judiciary for decades. However, a single replicable model of proportionality has not been consistently applied by the courts. This paper explores the differential application of proportionality in English law. It is argued that these differential approaches create doctrinal confusion and give rise to numerous shortcomings. These shortcomings include: (i) the a priori weighting of fundamental rights; (ii) undue deference to state institutions; and (iii) variable judicial scrutiny dependent upon the source of the rights in question. It will be argued here that the courts ought to adopt a common standard of proportionality review in all proceedings concerning fundamental rights. The viability of this approach will then be tested against existing case law.
Heterogeneity of Beliefs and Trade in Experimental Asset Markets
Authors: Carlé Tim A. , Lahav Yaron , Neugebauer Tibor , Noussair Charles N.
Published: December 2018

We investigate the relationship between traders’ expectations and market outcomes with experimental asset market data. The data show that those who have high price expectations buy more frequently and submit higher bids, and those who hold low price expectations sell more frequently and submit lower bids. Traders who have more accurate expectations achieve greater earnings. Simulations using only belief data reproduce the pricing patterns observed in the market well, indicating that the heterogeneity of expectations is a key to explaining market activity.
Government Intervention and Strategic Trading in the U.S. Treasury Market
Authors: Pasquariello Paolo , Roush Jennifer , Vega Clara
Published: December 2018

We study the impact of permanent open market operations (POMOs) by the Federal Reserve on U.S. Treasury market liquidity. Using a parsimonious model of speculative trading, we conjecture that i) this form of government interventionimprovesmarket liquidity, contrary to conclusions drawn by existing literature; and ii) the extent of this improvement depends on the market’s information environment. Evidence from a novel sample of Federal Reserve POMOs during the 2000s indicates that bid–ask spreads of on-the-run Treasury securitiesdeclinewhen POMOs are executed, by an amount increasing in proxies for information heterogeneity among speculators, fundamental volatility, and POMO policy uncertainty, consistent with our model.
Darwin's Heresy
Authors: Goodman Lenn E.
Published: December 2018

Challenged by Lord Kelvin's claims that earth and sun were too young to give evolution sufficient time to do its work, especially in the human case, where care for the weak blunts the edge of natural selection, Darwin leaned on Lamarckian thoughts to accelerate the process. The mental and moral traits crowning human distinctiveness, he urged, arose through sexual selection. But promiscuity, infanticide, early betrothals, and female drudgery undermined these effects in “savage races.” In the inevitable decline and ultimate extinction of the “melanin races” Darwin believed he could observe human evolution underway before his eyes.
Cognitive change in cognitive-behavioural therapy v. pharmacotherapy for adult depression: a longitudinal mediation analysis
Authors: Quigley Leanne , Dozois David J. A. , Bagby R. Michael , Lobo Daniela S. S. , Ravindran Lakshmi , Quilty Lena C.
Published: December 2018

Background

Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model.

Methods

The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models.

Results

Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant.

Conclusions

The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change.